UV light stimulated encapsulation and release by polyelectrolyte microcapsules

Advances in Colloid and Interface Science xxx (2013) xxx–xxx

CIS-01354; No of Pages 10

Contents lists available at ScienceDirect

Advances in Colloid and Interface Science

j ourna l homepage: www.e lsev ie r .com/ locate /c i s

UV light stimulated encapsulation and release bypolyelectrolyte microcapsules

Qiangying Yi 1, Gleb B. Sukhorukov ⁎,1

School of Engineering and Materials Science, Queen Mary University of London, London, United Kingdom

⁎ Corresponding author.E-mail address: [email protected] (G.B. Sukho

1 Tel.: +44 20 7882 5508; fax: +44 20 8981 9465.

0001-8686/$ – see front matter © 2013 Elsevier B.V. All rihttp://dx.doi.org/10.1016/j.cis.2013.11.009

Please cite this article as: Yi Q, Sukhorukov Gterface Sci (2013), http://dx.doi.org/10.1016

a b s t r a c t
a r t i c l e i n f o
Available online xxxx

Keywords:Polyelectrolyte microcapsulesStimuli responsiveEncapsulationReleaseUV irradiation

Layer-by-layer assembled polyelectrolyte capsules with well-controlled architectures and great versatility havebeen the subject of great interest, due to their unique advantages and tremendous potentials of being excellentcandidates in multidisciplinary fields. UV light responsive microcapsules, as one class of the stimuli responsivecapsules, possess the abilities to active their functionalities by responding to the UV stimulus remotely withoutrequirement of direct contact or interaction. Therefore, any advances in this field will be of great value for theestablishment of approaches to fabricate UV responsive polyelectrolyte capsules for desired uses. This reviewpresents current development of UV responsive capsules, with emphasis on the underlying design strategiesand their potential applications as delivery vesicles. In particular, UV-stimulated capsule functionalities, suchas cargo encapsulation, release and combined multifunctionalities by the multilayers, have been addressed.

© 2013 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 02. Encapsulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 03. Release . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 04. Multi-functionality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 05. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

1. Introduction

In recent years, great effort has been focused on development of thepotential vesicles/delivery systems with well-controlled structures andmodulated functionalities, benefitting from the fast developed impactand promising prospects of nanoscience and nanotechnology. Amongthe well-established methods, the layer-by-layer (LbL) assemblytechnique has attracted increasing interests and has been intensivelystudied as one of the most promising ways to fabricate carrier systems[1]. Specifically, LbL assembled capsules can serve as multifunctionalplatforms for desired uses, where the tunable carrier structure, shapeas well as mechanical properties could be integrated [2]. In addition tothe basic principle of the LbL fabrication process, recent studies have

rukov).

ghts reserved.

B, UV light stimulated encap/j.cis.2013.11.009

also investigated the prepared multilayers with varied architecturalproperties and future perspectives [3,4].

Significantly, the stepwise capsule fabrication process and multiplecombinations of complementary building blocks endow the formed cap-suleswith noteworthy potential and abilities to respond to numerous envi-ronmental stimuli. In return, environmental stimuli, such as pH,temperature, ionic strength and external energy fields, can be applied toregulate capsule properties, and hence to functionalize the capsule systems[5]. Recent research works have contributed to a better comprehension ofthe LbL capsule responsiveness with the emphasis on nature of capsulecomponents and shell architecture [5,6]. The appealing feature of develop-ing such stimuli-responsive capsules is their numerous stimuli-triggeredfunctionalities and potential applications in the fields ranging from medi-cine and pharmaceutics to chemical synthesis and catalysis [7–10].

Light addressable capsules, as a center interest of stimuli-responsivecapsules, offer the advantages by altering their physicochemical proper-ties remotely when exposed to light directly. For potential applicationsin biologicalfiled, near-infrared (NIR) lasers in thebio-friendly radiationwindow (700–1000 nm) are preferred, because of its high transmission

sulation and release by polyelectrolyte microcapsules, Adv Colloid In-

http://dx.doi.org/10.1016/j.cis.2013.11.009

mailto:[email protected]

Unlabelled image


Unlabelled image

http://www.sciencedirect.com/science/journal/00018686


2 Q. Yi, G.B. Sukhorukov / Advances in Colloid and Interface Science xxx (2013) xxx–xxx

and low scattering effect [11]. Electromagnetic frequency of this regionpredominately causes generation of local surface plasmon resonance(LSPR) oscillation at nanoparticle surface [12], which initiates lightscattering or heat locally as the result of energy decay [13]. Therefore,embedding of laser light absorbing nano-scale metal or metal oxideparticles into polyelectrolyte shells provides a photocontrollable wayto adjust capsule shell permeability [14]. Altering the shape [15] anddistribution state [16,17] of nanoparticles pushes forward the red-shiftof their light absorption positions toward longer wavelength region, inorder to meet the demands of (bio)medical uses. Proper controllednanoparticles generate a bigger surface area for the laser illumination,leading to the achievement of absorption coefficient increase by 5times [18] and a temperature rise up to 7 K in contrast to less than1 K of a single nanoparticle [19]. Based on this mechanism, LbL capsulescontaining noble metal nanoparticles (e.g. gold and silver) and IRabsorbing dye (IR-806) have been fabricated, and used to realize remotecontrol of capsule disruption in vitro [20,21]; similar work has also beensuccessfully conducted in vivo, where intracellular release of loadedcargo substances as well as cellular signaling and screening drugsagainst intracellular targets has been achieved by IR lasers withoutcausing severe damage to surrounding medium [19,22–24]. Unlike therelease triggered by biodegradation, the laser absorbing capsulesopens new window for single cell manipulation and site-specific drugdelivery and release. Together, the recent studies focusing on theoptically addressable capsules have well demonstrated the currentdevelopment, long-range outlook and possible limitation of thesecapsules for in vivo and in vitro uses [25].

Among the rich variety of light addressable vesicles, functionalitiesof UV-responsive vesicles can be accomplished upon exposure to exter-nal UV light. Regarding practical applications, sometime UV light withcontinuous wavelengths (e.g., sunlight) could be the only one availablestimulus to activate the system. Thus the use of the UV light could becrucially necessary and highly desirable. A broad range of smartfunctional UV light responsive micro-/nano-vesicle systems, in theform of polymeric micelles, gels and liposomes, has been developed[26]. However, to date, obviously there are only very few reportedstudies dealt with the preparation and further functionalization of theUV-responsive LbL capsules.

In this review,we present recent development of LbL assembled UV-responsive microcapsules, with particular emphasis on the investiga-tion of their potential functions, exploring their possibilities for cargoencapsulation and/or release in delivery domain. We propose thestrategies to build up microcapsules containing UV sensitive chromo-spheres/groups, and study on their underlying UV-stimulated chemicaltransitions.Moreover, the differences derived fromvaried combinationsof the complementary building blocks and capsule architectures are alsoexamined and discussed, in order to illustrate the possible influence oncapsule property changes triggered by external UV light.

2. Encapsulation

The primary functionality of the LbL capsules is encapsulation,whichstems from entrapment of cargo substances in capsules interior, in largecavities or ultrathin multilayer shells. Considering the stepwise capsulefabrication process, encapsulation of desired cargos can be carried out in

Scheme 1. Schematic representation of benzophenone-related crosslinking reaction in the cappolyanion and polycation.Reproduced from [40] with permission from the American Chemical Society.

Please cite this article as: Yi Q, Sukhorukov GB, UV light stimulated encapterface Sci (2013), http://dx.doi.org/10.1016/j.cis.2013.11.009

the duration of template preparation step (e.g., by co-precipitating withCaCO3 [27]) and/or after template removal procedure (e.g., by diffusingthrough porous shells [28]). After loading, themultilayer capsules couldprovide secure cargo storage; potential harmful effect from the outerenvironments could be shielded. In previous researchworks, the encap-sulation of the cargo substances such as proteins [27], DNA [29], en-zymes [30] and small inorganic materials [31] has been successfullydemonstrated.With regard to further application such asmodulated re-lease, methods that could be applied to realize cargo retention are alsorequired to shed light on long-term storage. However, the truth is thatthe fabricated capsules are commonly porous network-like structures,which are highly permeable to the substances with a molecular weightbelow 5 kDa [32]. In general, varied capsule preparation parameters, forexample ionic strength of polyelectrolyte solution, template employ-ment, building blocks and core removal condition, could influence theshell porosity, and hence affect shell permeability [4]. After capsulepreparation, for the obtained capsules with defined shell compositionand thickness, decrease of capsule shell porosity (mesh size) couldmin-imize or switch off the shell permeability. Strategies such as heat treat-ment [33], chemical crosslinking [34] and shell shrinking [35] have beendeveloped to achieve the goals. Analogous to other successful examplesof stimuli-responsive capsules [5,36,37], improved encapsulation couldalso be envisioned using the UV-responsive LbL capsules, for whichtheir shell porosity and multilayer arrangement can by adjusted byresponding to external UV light with suitable wavelength [35,38].

In particular, an interesting UV sensitive group is benzophenone(Ph2CO). The chemically stable benzophenone and its derivates havebeen widely used as photoactivatable reagents tomodify or reconstructthe remote C\H bonds in flexible molecular chains, even in the pres-ence of water [39]. Incorporating the benzophenone groups in polyionsenables the preparation of UV sensitive polyelectrolyte. For example,benzophenone-substituted poly(methacrylic acid) (PMA-BP, substitu-tion degree = ∼50%) can be prepared after introduction of the benzo-phenone chromospheres in poly(methacrylic acid). Sequentialdeposition of the negatively charged PMA-BP and positively chargedpoly(allylamine hydrochloride) (PAH) allowed fabrication of the UVcrosslinkable multilayer microcapsule (PAH/PMA-BP)4 [40]. Upon UVirradiation at 275 nm, the benzophenone groups reacted withunreactive C\H bonds in neighboring polymeric chains predominantly,leading to crosslinking within the assembled PAH/PMA-BP multilayers(Scheme 1).

Exposure of fabricated (PAH/PMA-BP)4 capsules to low intensity UVlight (5 mW·cm−2) initiated capsule shrinkage as a function of UV irra-diation time, as shown in Fig. 1 [40]. Typically, 15 min of UV irradiationshrunk the capsule size from original 5.12 ± 0.31 μm (Fig. 1a) to4.54 ± 0.30 μm (Fig. 1b). Extending UV irradiation duration, the(PAH/PMA-BP)4 capsule size was continuously decreased. An obvioussize reduction of about 30% in diameter was observed when the irradi-ation time reached 120 min (Fig. 1f). With the shrinkage of capsule, thecapsule shell appeared thicker and stronger with doubled shellthickness. The resulting capsules exhibited as denser spherical ball-like formations under the SEM observation (Fig. 1f).

These crosslinked capsules exhibited low permeability after UVinduced condensation, offering an alternative way for cargo encapsula-tion. As shown in Fig. 2, the confocal laser scanningmicroscopy (CLSM)

sule shells. *The photo-crosslinking won't influence the electrostatic interactions between


image of Scheme�1


Fig. 1. SEM images of (PAH/PMA-BP)4 capsules at various UV irradiation times. *Scale bar measures 2 μm.Reproduced from [40] with permission from the American Chemical Society.

3Q. Yi, G.B. Sukhorukov / Advances in Colloid and Interface Science xxx (2013) xxx–xxx

images illustrated the cargo encapsulation of (PAH/PMA-BP)4 capsulesin the presence of a AF488-dextran (10 kDa) [40]. In sharp contrast tothe high permeability of capsules without UV irradiation (Fig. 2b),15 min of the UV irradiation condensed the capsule shells and henceafford these crosslinked capsules ability to entrap fluorescent polymers,as seen by the green dots under CLSM observation (Fig. 2c).

Other UV-responsive microcapsules have been developed to encap-sulate the large molecular cargo substances effectively without losingtheir activities. Bédard et al. proposed a UV responsive microcapsulesystem to encapsulate the fluorescent macromolecules (10 kDa) viaUV-triggered azobenzene molecular isomerization [35]. Similar as wefound above, UV light can stimulate adjustment of capsule shell perme-ability, compact the capsule shells and hence realize the entrapment ofmacromolecules. However, one could notice that some of the capsuleswere still hollow without fluorescent polymer entrapped in theircavities. These results could be attributed to the not tightly sealedshell structures. As detected by nuclear magnetic resonance (NMR)cryoporometry technique, the polyelectrolyte multilayers are porousstructures, containing free water voids on the shells [41]. The occupiedhydration water in multilayers contributes the formation of pores oncapsule shells. In practice, these pores afford permeable multilayerswith specific substance cut-off values, allowing size-dependenttransport of cargo substances [3,42]. These studies correlated with theobserved hollow capsules indicated that the UV-induced chemicalchange, either in our PAH/PMA-BP system or in Bédard's azobenzenecontaining capsule system, was not adequate to close the pores on theshells, thus the fluorescent polymers escaped through the porous shellsor defects, even after UV-related shell modification.

Comparing with the macro- or large molecules, the low molecularweight substances (b1 kDa) are relatively smaller in size. Theoretically,the hydrodynamic radius (RH) of the small molecular dye (rhodamineand fluorescein) is approximately 1 nm or less [41,43]. Likewise, RH is

Fig. 2. CLSM images of cargo encapsulation of (PAH/PMA-BP)4 capsules in the presence of a AF4hollow capsules (a), can't be retained if washed directly (b), but can be encapsulated in the capsthe references to color in this figure legend, the reader is referred to the web version of this arReproduced from [40] with permission from the American Chemical Society.


2.5 nm for the fluorescent dextran (10 kDa) [33]. Comparatively,the pore size of the LbL assembled capsule shells is relativelylarge. For example, the microcapsules composed of four bilayersof poly(diallyldimethylammonium chloride) (PDADMAC, 200–350 kDa)and poly(styrenesulfonate) (PSS, 70 kDa) have the apparent shell poresize of about 13 nm [33]. Therefore, encapsulation of these small molecu-lar substances in multilayer capsule interiors is still a challenging task,although we have already decreased the pore size of (PAH/PMA-BP)4shells for macromolecule encapsulation.

To encapsulate small molecular substances, careful considerationshould be given. On the one hand, a controllable modification methodwould be used to compact or seal the capsule shells after cargo loading.For example, the UV-stimulated shell crosslinking would be favored todecrease the capsule shell mesh size. On the other hand, the shell com-ponents that expel water voids would carry less hydration water andable to minimize the size-dependent cargo transportation. Combingthese two aspects, the optimal capsules for small molecule encapsula-tion would be the ones who are intrinsically hydrophobic multilayerswith fewer and smaller pores on the shells. Strategically, we proposedthe diazoresin (DAR) containing microcapsules to overcome this issue.Positive charges of DAR could facilitate the stepwise polyion depositionbased on electrostatic interactions, and the special reactive diazoniumcompounds (\N+`N:) could participate in the UV induced photolysisrapidly [44]. As shown in Scheme 2, two types of the DAR capsule sys-tems were proposed [45]. Briefly, the (Nafion/DAR)4 microcapsuleswere made of polycation DAR and the polyanion Nafion which consistsof a perfluorinated backbone and sulfonic acid groups in the side chains[46]; the another DAR8 single component microcapsule system wasfabricated with single type of DAR polymers through LbL assemblyand charge reversal process [47,48].

Upon exposure to a 380 nm UV light, the diazonium group of DARcould be activated rapidly to formphenyl cation and then be substituted

88-dextran. *Before UV irradiation, the fluorescent polymer (green) can permeate into theules after 15 min of UV irradiation, even after severalwash steps (c). (For interpretation ofticle.)


image of Fig.�1

image of Fig.�2


Scheme 2. Photolysis induced small molecule encapsulation in (a) Nafion/DAR and (b) DAR single component multilayer capsules.Reproduced from [45] with permission from the American Chemical Society.


by nucleophilic groups, for example the sulfonate of Nafion or diazo-sulfonate of the charge reversedDAR (Scheme2). Based onUV triggeredphotolysis, the paired ionic chargeswere eliminated or converted to co-valent bonds, offering a novel method to crosslink the built multilayers[45]. This chemical transition here mainly involved the in situ photoly-sis, thus no obvious capsule size change could be found in the twoDAR capsule systems. The most essential change of the capsule shellproperty here was the greatly decreased shell permeability, due to theionic charge elimination and resulting hydrophobic phenyl ring richstructures. This change was confirmed by the water wettabilitymeasurement. After UV irradiation (55 mW·cm−2, 10 min), theaverage water contact angle was changed from 54 ± 3.0° to78 ± 1.0° for (Nafion/DAR)4 and from 38 ± 4.0° to 49 ± 4.0° for theDAR8 multilayers, respectively [45].

Without ionic charges, these irradiated multilayer capsules becamecrosslinked and carried less water voids, thus diffusion of encapsulatedcargo substances could be minimized. In other words, the irradiatedcapsules could act as “sealed”micro-containers for cargo encapsulation.An typical example of the macromolecule encapsulation was demon-strated by the (Nafion/DAR)4 microcapsules. After UV irradiation(55 mW·cm−2, 10 min), the (Nafion/DAR)4 microcapsules allowed along storage time of AF488-dextran (10 kDa) for weeks, as shown inFig. 3 [45]. The retained fluorescent polymers exhibited a relativelystrong signal, which exceeded the user-defined value (250 units) inthe fluorescence channel (Fig. 3a). Over two weeks, encapsulated

Fig. 3. CLSM images of AF488-dextran (10 kDa) encapsulation in (Nafion/DAR)4 microcapsul(b). The line scan insets showed relative fluorescent intensity in capsules.(Reproduced from [45] with permission from the American Chemical Society).


AF488-dextran gradually penetrated out, leading to reduction offluorescent signal intensity (~200 units) (Fig. 3b).

The pronounced change on capsule permeability also paves the wayfor using these LbL capsules toward small molecule encapsulation. Asshown in Fig. 4, these DAR containing capsules permitted successfulencapsulation of small molecular rhodamine B (RhB, Mw = 479) [45].After UV irradiation (55 mW·cm−2, 10 min), these capsules showedgreat ability to retain the RhBmolecules and slowed down their releasein long duration. Specifically, the (Nafion/DAR)4 microcapsules showeda better dye encapsulation efficiency than others, where 690 fg RhBwasencapsulated in one capsule initially, and then 38% of the RhB stillremained over 11 days after capsule sealing. Promisingly, these DARmicrocapsules can be used as micro-carriers for small molecule encap-sulation and modulated release.

It is worth noting that, in previous works, successful loading ofsmall molecular rhodamine 6G (Rh6G, positively charged) has beenperformed, through electrostatic interaction with opposite chargedpolymeric complex [49] or precipitation in the capsule cavities mediat-ed by environmental pH value [50]. Unlike the two methods, here theencapsulation of RhB was based on shell sealing, triggering remotelyby UV light. The charming advantage of this method is that other lowmolecularweight substances could be encapsulated in theDAR capsuleswithout requirement of their ionic charges or environmental pH adjust-ment. Moreover, the UV-induced rapid capsule sealing would beextraordinarily useful in terms of catching small molecules in the

es. *These images were captured after irradiation (a), and over 2 weeks after irradiation


image of Scheme�2

image of Fig.�3


Fig. 4. CLSM images of RhB containing (Nafion/DAR)4 (a) and DAR8 (b) microcapsules after 10 min of UV irradiation. Image (c) showed the RhB encapsulated DAR microcapsules before(left) and after (right) centrifugation at 4500 rpm for 5 min. *The line scan insets showed relative fluorescent intensity in capsules; the arrow showed a broken capsule, in which no RhBcould be retained.Reproduced from [45] with permission from the American Chemical Society.


biological environment, where the small molecules carrying useful(bio-)information can be captured, followed by their proteomicsanalysis.

3. Release

Release, as the ultimate aim in the field of delivery, is to liberate theentrapped substances at intended location in desired manners. One ofthemost straightforwardmethods to achieve release is to destroy integ-rity of the carrier system. Two distinct routes of releasing have beendemonstrated in either instant or sustainedway. In general, mechanicaldeformation of capsules by means of remote physical influences(e.g., near-infrared laser) [51] or degradation (e.g., enzymatic reactionsor hydrolysis) [52,53] can realize the burst release of encapsulatedsubstances. On the contrary, the slow release over an extended periodcan be achieved by the cargo diffusion through porous structures withadjustable shell permeability [54].

As for the UV-responsive capsules discussed here, strategies areexpected to affect capsules' nano- and/or micro-structures remotelyunder UV irradiation. Not surprisingly, UV ablation effect can be appliedto break LbL capsules directly in water. Exposure of the (PAH/PSS)4microcapsules to pulsed UV laser (355 nm) at high energy density(70 mJ·cm−2 or above) led to severely capsule damage [55]. Usingthis method, the capsule breakage is attributed to generated lightpressure and plasma on capsule shells, no direct UV absorption of theshell constituents is therefore required. However, damage to the cargosubstances might be involved due to the high energetic process byusing pulsed UV laser [55]. Alternatively, other milder UV illuminationconditions, such as using of UV source with continuous wavelengths,would be preferable for specific applications.

As a strategic approach, employments of UV-cleavable componentsas building blocks would facilitate the breakage of fabricated vesicles.o-Nitrobenzyl (ONB) and derivatives, as one type of the photo-cleavable groups, have beenwidely studied as the typical examples [56].Exposing self-assembled vesicles (mainly micelles) to near-UV light(N320 nm) would initiate a rapid ester bond cleavage, which willfurther lead to decoupling of themultilayer system, providing full activ-ities of the two departed functional segments. As reported previously,after UV irradiation, the carriers composed of amphiphilic polymersdisintegrated, generating small micellar-like structure, and simulta-neously released their encapsulated substances such as hydrophilicmolecules [57] and DNA [58]. Ideally, introducing the ONB componentinto polyelectrolyte chains (backbones or side chains with ioniccharges)would provide opportunity to deconstruct fabricatedmultilay-er shells. Consequently, UV light could be used to govern capsule shell


disassembly selectively and gradually. Unfortunately, no present workhas been associated with the ONB containing LbL capsule system yet.

Polymers containing azobenzene (PhN_NPh) groups are the well-studied photo-responsive building blocks for various uses [59]. Besidesthe famous trans–cis photoisomerization, the azobenzene molecularalignment could be conducted by UV light due to possible influencesoriginated from the interacted chemical environment. Incorporatingthe robust azobenzene molecules in building blocks offers anotherapproach to break the assembled multilayer integrity. Specifically,when irradiated with light of the appropriate wavelength, azobenzenewould generate the styled (end-to-end or plane-to-plane) aggregatesin the azobenzene containing system [60,61]. Assembled azobenzeneaggregates or clusters would cause catastrophic destruction to thefabricated shell-like formations [61,62].

When the photoactive polyanion poly{1-4[4-(3-carboxy-4-hydroxyphenylazo)benzenesulfonamido]-1,2-ethanediyl sodium salt}(PAZO, ~100 kDa) containing azobenzene segments in the side chainsand polycation Poly(diallyl dimethyl ammonium chloride) (PDADMAC,200–350 kDa) bearing five-member heterocyclic rings and ioniccharges were used for LbL assembly, the capsule shell disruption wasrealized upon UV exposure [63]. As shown in Fig. 5, UV irradiation(55 mW·cm−2) generated a gradual shell swelling–breakage processof the (PDADMAC/PAZO)4 microcapsules. Briefly, 10 min of UV irradia-tion increased the capsule size from5.12 μmtomore than 7 μm(Fig. 5a,b). With increase in the UV irradiation time, more and more capsulesbecame swollen and apparent capsule debris (white dots) was ob-served surrounding these capsules, indicating capsule breakage locally.Extending the UV irradiation time to 2 h, no intact capsule can be found,only the split capsule debris and some needle-like formations wereobserved under SEM observation (Fig. 5d).

In the PDADAMC/PAZO system, the rigid PDADAMC chains facilitat-ed azobenzene molecular motion of interacted PAZO in domain insteadof the azobenzene conformational change in plane. UV–visible spectros-copy measurements recorded the UV-induced azobenzene aggregationprocess. As shown in Fig. 6a, accompanying with the maximumabsorbance decrease, UV irradiation (55 mW·cm−2, 2 h) launched ared-shift by 17 nm toward longer wavelength region, demonstratingthe J-styled aggregates in PDADMAC/PAZO capsule system [64]. As aconsequence, these individual end-to-end self-organized azobenzenemolecules led to polymer chainmotions locally, which further exhibitedas phase separation of adjacent domains due to anisotropic orientedaverage aggregate directions (Fig. 6b) [63]. Accumulated azobenzenemolecular realignment effect caused the (PDADMAC/PAZO)4 capsulesswelling and breakage. Similar strategies have been applied todeconstruct the assembled shell-like formations such as photosensitiveliposomes [65] and polymersomes [22] for drug delivery use, and


image of Fig.�4


Fig. 5. SEM images of (PDADMAC/PAZO)4 capsules after UV irradiation of 0 (a), 10 min (b), 60 min (c) and 120 min (d).Reproduced from [63] with permission from the Royal Society of Chemistry.


also the PDADMAC/PAZO capsule systems, where the release of encap-sulated cargo (BSA, 66 kDa) was speeded up [63]. Generally, suchazobenzene containing multilayer capsules could have the potential tobe developed into a remote releasing system, where the shells can beopened upon continuous UV exposure.

Fig. 6. (a) UV–visible spectra of (PDADMAC/PAZO)4 microcapsule suspensions before (–), and aof (PDADMAC/PAZO)4 microcapsule disruption induced by UV irradiation.Reproduced from [63] with permission from the Royal Society of Chemistry.


Aggregations of other chromospheres in self-assembled multilayersystems also demonstrated the potential to realize LbL capsule break-age. Bédard et al. reported the photoactive microcapsules consisting ofPAH, PSS and the tetrapyrrolic dye meso-tetrakis (4-sulfonatophenyl)porphine (TPPS) [66]. In this system, the TPPS is interacted with PAH

fter UV irradiation for 30 min (■), 60 min (Δ) and 120 min (×). (b) Schematic illustration


image of Fig.�5

image of Fig.�6



as a teranion and showed H-styled aggregates in multilayers. Interest-ingly, non-coherent light from a xenon lamp (150 W) showed noobvious damage to capsules, even after 1 hour long exposure. However,the laser treatment (532 nm, 70 mW) caused rapid disruption ofTPPS containing capsule shells in the presence of an oxidizing agent(H2O2). Unlike the capsule mechanically destroyed based on eitherlaser-induced LSPR effect of IR-absorbing dye (e.g., IR-806) [20] orazobenzene molecular realignment [63], here the excited TPPSmolecules induced the highly reactive hydroxyl radicals by transferringenergy to surrounding H2O2, then generated active oxygen speciesinfluenced the interactions of paired polyelectrolytes, leading to capsuledisruption.

UV sensitive components/groups in the building blocks are some-times not necessary to control the integrity of the capsules. Increasingsolution ionic strength provides another route to swell/disassemblythe capsules, by shielding the charges of surrounding polyelectrolytes.This process can also be UV-controllable through addition of UV-decomposable multicovalent counterions in capsule suspensions. Asreported by Xu et al., the permeability of the 18-armed polymeric mi-crocapsules could be altered remotely by UV-induced decompositionof the trivalent hexacyanocobaltate ions ([Co(CN)6]3−) into mono-and divalent ions [67]. With the generation of more free ions, interac-tions between polycations and polyanions are therefore weakened,leading to swelling of capsule shells and releasing of cargo substances.UV induced environmental pH change provides another alternativeroute to adjust capsule shell permeability. As proposed by Koo et al.,when the capsules are exposed under UV irradiation (254 nm),polyelectrolyte multilayer capsules containing photoacid generators(PAGS) enable an optically addressable release of protons within 40 s[68]. Consequently, liberated protons loosened the paired polyions byenhancing themutual repulsion between the layers, resulting in capsuleswelling and further cargo release. Another similar case reported byErokhin et al. demonstrated the capsule shell pore opening, where thelocal pH variation was attributed to the low intensity daylight-drivenproton pumping effect of the bacteriorhodopsin incorporated in capsuleshell [69].

4. Multi-functionality

As discussed above, the UV light could be used to activate thefunctionalities of the built LbL microcapsules remotely, demonstratingas improved cargo encapsulation or modulated release respectively. Infact, to develop an intelligent delivery system is of vitally complicatedpractice. Sometimes, capsules are required to respond not only to singleexternal stimulus. Therefore, effective methods for fabrication of capsule

Fig. 7.Diameter ofmicrocapsules as a function of pH (a), and LCSM images of (PAH/PMA-BP)4 atare dissolved.Reproduced from [40] with permission from the American Chemical Society.


systems that can integrate two or more stimuli-responsiveness willcomplement ongoing efforts to advanced smart vesicle systems.

Considering the stepwise polyelectrolyte deposition process, selec-tion of the complementary building blocks would help the governmentof the capsule properties. Employing weak polyelectrolytes for LbL as-sembly, fabricated capsuleswould be endowedwith pH responsiveness.Proper preservation of the ionic groupswould enable the capsules to an-swer external pH stimulus. As a practical matter, such pH-responsiveproperty allowsmodulated cargo release through the shrunk or swollencapsule shells after cargo encapsulation, by adjusting the dissociationequilibrium of corresponding weak polyelectrolytes. As we found inthe above work, the benzophenone-related crosslinking could decreasethe shell permeability of (PAH/PMA-BP)4 microcapsules, allowingencapsulation of macromolecular substances. Specially, unlike theamidation reaction of \COOH and \NH2 groups [70], this methodshowed great capability to stabilize the capsules through benzophe-none-related hydrogen abstraction and further recombination.Avoiding consumption of the interacted ionic groups of correspondingpolyelectrolytes, UV-crosslinked capsule shells still possessed pH re-sponsiveness. Adjusting the environmental pH value towards alkalineor acidic region influenced the electrostatic interaction of the PAH/PMA-BP complex, demonstrating as capsule shell swelling or shrinkagein a broad pH region (Fig. 7a) [40]. Thus, by answering to two differentexternal stimuli (i.e. UV and pH), this PAH/PMA-BP capsule system canbe developed as two-channel controllable delivery vesicles. The encap-sulation of cargo substances (primarily with large molecular weight) insteady micro-containers can be achieved by simple UV irradiation; andthen modulated release can be realized through adjustment of capsuleshell stability by varying the environmental pH.

Another typical feature of benzophenone-related crosslinking is thegreat stability of the capsules after UV crosslinking. As shown in Fig. 7b,the UV crosslinked (PAH/PMA-BP)4 was quite stable, even in extremepH conditions where the other two non-crosslinked capsules weredissolved [40]. Enhancement of the capsule physical stability againstdissolution in extreme pH conditions is very useful, due to potentialapplication in physiological environment. For example, disulfide bondcross-linked nanocapsules were stable at low pH (1.4), and hencecould provide secure storage of protein drugs against destruction bygastric acid in gastric cavity [71].

Unlike the specified capsule shrinkage and swelling triggered by in-dividual UV and pH treatments, the same stimuli could also be used toactivate multifunctionalities of the capsule system. Ideally, the sameUV light could be applied to functionalize diverse multilayer propertiesin one capsule system. Typically, one specific layer could be used torealize shell sealing for cargo encapsulation; the other layers could be

pH 2 and pH 12 (b). *The gray areas indicate the regionswhere the un-irradiated capsules


image of Fig.�7



used to break the whole shell for release. Therefore, the cargo encapsula-tion and successive adjustable release could be activated selectivelywhenthe specific layers are irradiatedwith light of the appropriatewavelength.The complex microcapsule system (PDADMAC/PAZO)4–(DAR/Nafion)2composed of two types of functional multilayers bearing oppositefunctional UV sensitive groups/components was developed as the clas-sic example [72]. Generally, UV source with the continuous wavelengthcould accomplish DAR/Nafion layers sealing in minutes and the succes-sive PDADMAC/PAZO layers rupture in hours. As shown in Fig. 8, theSEM images revealed corresponding complex capsule size and mor-phology changes after exposure to various UV irradiation times. Undera given UV irradiation condition (55 mW·cm−2), the complex capsulesexhibited a time-dependent swelling process. After 3 h of UV irradia-tion (Fig. 8c), almost all of the capsules greatly increased their sizeand some of them possessed a size of up to 8 μm. Meanwhile, obviouspores up to 100 nm in diameter were observed on the shells. Onewould notice that the capsule morphology change of the complexcapsuleswas slightly different from that of themicrocapsules composedof pure PDADMAC/PAZO system, where most of the spherical capsuleswere torn into pieces (Fig. 5d). This difference could be attributed tothe interplay of the PAZO in different multilayers. On the one hand, in-corporating with the PDADAMC allowed UV conducted azobenzenemolecular realignment, which mainly caused the mechanical damageof the fabricated PDADMAC/PAZO shells locally. On the other hand,photolysis of PAZO and DAR polymers led to crosslinked layers. PossibleUV triggered azobenzene motion in PDADMAC/PAZO layers wastherefore restricted, while the crosslinking effect in the multilayers(DAR/Nafion, PAZO/DAR)was strengthened. Consequently, the intrinsicchemical transition here primarily led to swollenmicrocapsules insteadof spilt pieces.

As discussed above, capsule shell sealing could be accomplishedrapidly; 10 min of UV irradiation at 55 mW·cm−2 was energeticenough to seal the DAR/Nafion layers without causing obviousshell damage (Fig. 8b), providing adequate capability to encapsulatecargo substances. Successful encapsulation of fluorescent substances,fluorescein (Mw = 332), AF488-dextran (10 kDa) and TRITC-dextran(500 kDa), has been carried out in our work. Specially, one shouldnotice that the complex capsules were fabricated firstly, and thenincubated with fluorescent polymers. Therefore encapsulation of cargowith variedmolecularweights (from 332 to 500 kDa) not only revealedthe high permeation of the fresh fabricated complex capsule shells, but

Fig. 8. Size changes of complex capsules after UV irradiation. *Capsule diameters anddistributions were expressed as mean ± SD of at least 30 capsules per sample of randommeasurement of SEM images. The insets showed the typical image of the capsules before(a) and after UV irradiation for 10 min (b) and 3 h (c).Reproduced from [72] with permission from the American Chemical Society.


also confirmed UV-induced shell sealing effect, which was demonstrat-ed as dramatically decreased shell permeability.

After cargo loading, successive release was performed upon long-term UV exposure [72]. As shown in Fig. 9, the resulting encapsulationof AF488-dextran in complex capsules was visualized as bright dotsunder CLSM observation (Fig. 9a). Several hours of UV irradiationcaused severe damage to the complex capsules, and stimulated therelease of fluorescent dextran through the generated pores or crackson shells (Fig. 9b). Generally, for one sealed complex capsule, 1.07 pgof AF488-dextran can be entrapped in the interior. Comparing withthe non-irradiated capsule group, where the dye release was primarilybased on diffusion, the irradiated capsule group demonstrated a muchfaster dye release rate. After 7 h of UV irradiation, 70.5% of the encapsu-lated fluorescent polymers were released, whereas there was only 31%release efficiency found in the non-irradiated ones.

Onemight suggest that similar dual functional effect would be stim-ulated by the light in other wavelength range, for example visible andinfrared (IR) regions. Interestingly, for the frequently studied light re-gion (200–1200 nm), UV light having shorter wavelength and higherenergy is the most often used radiation in the photochemical reactions,to excite or reactive most molecular covalent bonds and atomic valenceelectrons of functional building blocks. Almost all the current researchworks primarily employ the UV sensitive compounds to achieve lightaddressable vesicle sealing or crosslinking. Sometimes the visible lightcould be used to relax or push backward the UV induced effect. Typicalexample has beenwell demonstrated in azobenzene containing system,where the tran–cis conformational change of azobenzene derives couldbe irreversible when the compounds are exposed to UV light or visiblelight alternatively [59]. As for the IR light, it normally conducts vesicledisruption, working together with embedded IR sensitive nanoparticleor dyes, due to generated LSPR effect. Therefore, the critical issue ofusing visible or IR light to realize both vesicle shell sealing and furtherbreakage focuses predominantly on the development of strategy todecrease shell porosity firstly. Photopolymerization would be electedas a convenient approach. In theory, by introducing proper visible/IR ab-sorbing compounds, it is possible to seal the capsule shells throughbuilding block polymerization. In practice, light with long wavelength(N nm) is much lower energetic than the UV light (b400 nm) due tothe Planck–Einstein equation (E = hc / λ), thus it would be quite diffi-cult and complicated to achieve the goal by using the light only; some-times other external assistance is required. It is very easy to speculatethis from the chemical aspect, for example visible light sensitive dyes(e.g., multi-cationic monomethine) could be used as high efficientinitiators to realize free radical polymerization of the buildingblocks containing arylate group; related photoinitiating ability can beenhanced by adding a second co-initiator [73]. Similarly, IR sensitivedyes (e.g., cyanine) can initiate the photopolymerization of vesiclebuilding block (containing ethylenically unsaturated compounds),with the addition of specifically radical generators (e.g., organoboroncompounds) [74].

5. Conclusions

In summary, this reviewmainly devoted to the recent developmentof the UV light responsive microcapsules fabricated by LbL assembly, inorder to explore new UV light addressable vehicles for the purpose ofcargo encapsulation and release. This review contributes to existingknowledge of UV-active LbL capsules by providing the findings ofcapsule changes on mechanical properties and also the underlyingchemical transitions. The potential applications of fabricated capsulesfor encapsulation and/or release were investigated, which wereachieved by applying of externally activation from UV light with suit-able wavelengths. UV induced capsule shrinkage could be applied totighten capsules for macromolecule encapsulation remotely (e.g., ben-zophenone related crosslinking). Moreover, successful small moleculeencapsulation was demonstrated in tightly sealed shells, benefiting


image of Fig.�8


Fig. 9. CLSM images of AF488-dextran encapsulation in complex (top panel) and (DAR/Nafion)4 (bottom panel) capsules right after shell sealing (a, c) and after 7 h of additional UVirradiation (b, d). *The line scan insets showed relative fluorescent intensity in capsules; the symbol ↗ represented collapsed capsules in water.Reproduced from [72] with permission from the American Chemical Society.


from the obtained water voids expelling shell structures after ioniccharge elimination (e.g., diazonium related photolysis in Nafion/DARsystem). Incorporating different functional components in the buildingblocks, UV light could be applied to stimulate breakage of the fabricatedcapsules, and this method could be used for modulated release of theencapsulated cargo. Typical example has been demonstrated in thePDADMAC/PAZO capsule system, where UV light triggered J-styledorientation of the azobenzene segments locally, leading to damage ofthe capsule integrity. Strategically, combination of the UV sensitivecomponents bearing opposite functions endows the specific polyelec-trolyte layers with different potential functionalities. Specially, complexcapsules containing both azobenzene and diazonium groups wereinvestigated for realization of the UV stimulated encapsulation andsuccessive release.

Hopefully, these UV-responsive capsules could serve as vesicles forthe development of new optically active systems, especially the UVlight active systems, to which abundant light (e.g. sunlight) could be in-troduced. Predicted applications could potentially be found in the fieldssuch as drug delivery, micro-reactor and photocatalysis to environmen-tal science,material surface science, and agricultural and cosmetic areas,benefiting from one or more light induced functionalities of suchoptically active systems. Promisingly, these brilliant ideas proposed inthe domain of UV responsive LbL capsules could be extended to


fabrication of other light addressable smart delivery systems, wherecontrollable encapsulation and/or release based solely on optical stimulicould be performed.

Acknowledgments

The author Q.Yi appreciates the financial support by the SEMS DTAstudentship (SEMS, QMUL) for her Ph.D. study.

References

[1] Decher G. Fuzzy nanoassemblies: toward layered polymeric multicomposites.Science 1997;277:1232–7.

[2] del Mercato LL, Rivera-Gil P, Abbasi AZ, Ochs M, Ganas C, Zins I, et al. LbL multilayercapsules: recent progress and future outlook for their use in life sciences. Nanoscale2010;2:458–67.

[3] Schönhoff M, Ball V, Bausch AR, Dejugnat C, Delorme N, Glinel K, et al. Hydration andinternal properties of polyelectrolyte multilayers. Colloids Surf A Physicochem EngAspect 2007;303:14–29.

[4] Klitzing R. Internal structure of polyelectrolyte multilayer assemblies. Phys ChemChem Phys 2006;8:5012–33.

[5] Delcea M, Möhwald H, Skirtach AG. Stimuli-responsive LbL capsules and nanoshellsfor drug delivery. Adv Drug Deliv Rev 2011;63:730–47.

[6] Glinel K, Déjugnat C, Prevot M, Schöler B, Schönhoff M, Klitzing R. Responsivepolyelectrolyte multilayers. Colloids Surf A Physicochem Eng Aspect 2007;303:3–13.

[7] De Cock LJ, De Koker S, De Geest BG, Grooten J, Vervaet C, Remon JP, et al. Polymericmultilayer capsules in drug delivery. Angew Chem Int Ed 2010;49:6954–73.


http://refhub.elsevier.com/S0001-8686(13)00162-0/rf0005
















image of Fig.�9



[8] Fakhrullin RF, Lvov YM. “Face-lifting” and “make-up” for microorganisms: layer-by-layer polyelectrolyte nanocoating. ACS Nano 2012;6:4557–64.

[9] Shutava TG, Balkundi SS, Vangala P, Steffan JJ, Bigelow RL, Cardelli JA, et al. Layer-by-layer-coated gelatin nanoparticles as a vehicle for delivery of natural polyphenols.ACS Nano 2009;3:1877–85.

[10] Skirtach AG, De Geest BG, Mamedov A, Antipov AA, Kotov NA, Sukhorukov GB. Ultra-sound stimulated release and catalysis using polyelectrolyte multilayer capsules. JMater Chem 2007;17:1050–4.

[11] Weissleder R. A clearer vision for in vivo imaging. Nat Biotechnol 2001;19:316–7.[12] Boisselier E, Astruc D. Gold nanoparticles in nanomedicine: preparations, imaging,

diagnostics, therapies and toxicity. Chem Soc Rev 2009;38:1759–82.[13] Jain PK, Huang X, El-Sayed IH, El-Sayed MA. Noble metals on the nanoscale: optical

and photothermal properties and some applications in imaging, sensing, biology,and medicine. Acc Chem Res 2008;41:1578–86.

[14] Skirtach AG, Karageorgiev P, Bédard MF, Sukhorukov GB, Möhwald H. Reversiblypermeable nanomembranes of polymeric microcapsules. J Am Chem Soc2008;130:11572–3.

[15] Skirtach AG, Karageorgiev P, De Geest BG, Pazos‐Perez N, Braun D, Sukhorukov GB.Nanorods as wavelength-selective absorption centers in the visible and near-infrared regions of the electromagnetic spectrum. Adv Mater 2008;20:506–10.

[16] Skirtach A, Dejugnat C, Braun D, Susha A, Rogach A, Sukhorukov G. Nanoparticlesdistribution control by polymers: aggregates versus nonaggregates. J Phys Chem C2007;111:555–64.

[17] Parakhonskiy B, Bedard M, Bukreeva T, Sukhorukov G, Mohwald H, Skirtach A.Nanoparticles on polyelectrolytes at low concentration: controlling concentrationand size. J Phys Chem C 2010;114:1996–2002.

[18] Kreibig U, Genzel L. Optical absorption of small metallic particles. Surf Sci1985;156:678–700.

[19] BédardMF, Braun D, Sukhorukov GB, Skirtach AG. Toward self-assembly of nanopar-ticles on polymeric microshells: near-IR release and permeability. ACS Nano2008;2:1807–16.

[20] Skirtach AG, Antipov AA, Shchukin DG, Sukhorukov GB. Remote activation of capsulescontaining Ag nanoparticles and IR dye by laser light. Langmuir 2004;20:6988–92.

[21] Angelatos AS, Radt B, Caruso F. Light-responsive polyelectrolyte/gold nanoparticlemicrocapsules. J Phys Chem B 2005;109:3071–6.

[22] Pavlov AM, Sapelkin AV, Huang X, P'ng KMY, Bushby AJ, Sukhorukov GB, et al.Neuron cells uptake of polymeric microcapsules and subsequent intracellularrelease. Macromol Biosci 2011;11:848–54.

[23] Gregersen KA, Hill ZB, Gadd JC, Fujimoto BS, Maly DJ, Chiu DT. Intracellulardelivery of bioactive molecules using light-addressable nanocapsules. ACS Nano2010;4:7603–11.

[24] Palankar R, Skirtach AG, Kreft O, Bédard M, Garstka M, Gould K, et al. Controlled in-tracellular release of peptides frommicrocapsules enhances antigen presentation onMHC class I molecules. Small 2009;5:2168–76.

[25] Antipina MN, Sukhorukov GB. Remote control over guidance and release propertiesof composite polyelectrolyte based capsules. Adv Drug Deliv Rev 2011;63:716–29.

[26] Alvarez-Lorenzo C, Bromberg L, Concheiro A. Light-sensitive intelligent drug deliverysystems. Photochem Photobiol 2009;85:848–60.

[27] Volodkin DV, Larionova NI, Sukhorukov GB. Protein encapsulation via porous CaCO3

microparticles templating. Biomacromolecules 2004;5:1962–72.[28] Shchukin DG, Sukhorukov GB. Selective YF3 nanoparticle formation in polyelectro-

lyte capsules as microcontainers for yttrium recovery from aqueous solutions. Lang-muir 2003;19:4427–31.

[29] Zelikin AN, Becker AL, Johnston AP, Wark KL, Turatti F, Caruso F. A general approachfor DNA encapsulation in degradable polymer microcapsules. ACS Nano2007;1:63–9.

[30] Caruso F, Trau D, Möhwald H, Renneberg R. Enzyme encapsulation in layer-by-layerengineered polymer multilayer capsules. Langmuir 2000;16:1485–8.

[31] Shchukin DG, Sukhorukov GB. Nanoparticle synthesis in engineered organic nano-scale reactors. Adv Mater 2004;16:671–82.

[32] Sukhorukov GB, Brumen M, Donath E, Möhwald H. Hollow polyelectrolyte shells:exclusion of polymers and donnan equilibrium. J Phys Chem B 1999;103:6434–40.

[33] Köhler K, Sukhorukov GB. Heat treatment of polyelectrolyte multilayer capsules: aversatile method for encapsulation. Adv Funct Mater 2007;17:2053–61.

[34] Kozlovskaya V, Kharlampieva E, Mansfield ML, Sukhishvili SA. Poly (methacrylicacid) hydrogel films and capsules: response to pH and ionic strength, and encapsu-lation of macromolecules. Chem Mater 2006;18:328–36.

[35] Bédard M, Skirtach AG, Sukhorukov GB. Optically driven encapsulation using novelpolymeric hollow shells containing an azobenzene polymer. Macromol RapidCommun 2007;28:1517–21.

[36] Skirtach AG, Yashchenok AM, Möhwald H. Encapsulation, release and applications ofLbL polyelectrolyte multilayer capsules. Chem Commun 2011;47:12736–46.

[37] De Geest BG, Sanders NN, Sukhorukov GB, Demeester J, De Smedt SC. Release mech-anisms for polyelectrolyte capsules. Chem Soc Rev 2007;36:636–49.

[38] Katagiri K, Matsuda A, Caruso F. Effect of UV-irradiation on polyelectrolyte multilay-ered films and hollow capsules prepared by layer-by-layer assembly. Macromole-cules 2006;39:8067–74.

[39] Dorman G, Prestwich GD. Benzophenone photophores in biochemistry. Biochemis-try 1994;33:5661–73.

[40] Yi Q, Wen D, Sukhorukov GB. UV-crosslinkable multilayer microcapsules made ofweak polyelectrolytes. Langmuir 2012;28:10822–9.

[41] Dong W-F, Ferri JK, Adalsteinsson T, Schönhoff M, Sukhorukov GB, Möhwald H.Influence of shell structure on stability, integrity, and mesh size of polyelectrolytecapsules: mechanism and strategy for improved preparation. Chem Mater2005;17:2603–11.


[42] Jin W, Toutianoush A, Tieke B. Size-and charge-selective transport of aromaticcompounds across polyelectrolyte multilayer membranes. Appl Surf Sci 2005;246:444–50.

[43] Ibarz G, Dähne L, Donath E, Möhwald H. Resealing of polyelectrolyte capsules aftercore removal. Macromol Rapid Commun 2002;23:474–8.

[44] Cao W, Ye S, Cao S, Zhao C. Novel polyelectrolyte complexes based on diazo-resins.Macromol Rapid Commun 1997;18:983–9.

[45] Yi Q, Sukhorukov GB. Photolysis triggered sealing of multilayer capsules to entrapsmall molecules. ACS Appl Mater Interfaces 2013;5:6723–31.

[46] Dai Z, Möhwald H. Highly stable and biocompatible nafion-based capsules with con-trolled permeability for low-molecular-weight species. Chem Eur J 2002;8:4751–5.

[47] Laschewsky A, Mayer B, Wischerhoff E, Arys X, Bertrand P, Delcorte A, et al. Anew route to thin polymeric, non-centrosymmetric coatings. Thin Solid Films1996;284:334–7.

[48] Yi Q, Sukhorukov GB. Single component diazo-resin microcapsules for encapsulationand triggered release of small molecules. Part Part Syst Charact 2013;30:989–95.

[49] Liu X, Gao C, Shen J, Möhwald H. Multilayer microcapsules as anti-cancer drug deliv-ery vehicle: deposition, sustained release, and in vitro bioactivity. Macromol Biosci2005;5:1209–19.

[50] Sukhorukov G, Dähne L, Hartmann J, Donath E, Möhwald H. Controlled precipitationof dyes into hollow polyelectrolyte capsules based on colloids and biocolloids. AdvMater 1999;12:112–5.

[51] Gil PR, del Mercato LL, del_Pino P, Muñoz_Javier A, ParakWJ. Nanoparticle-modifiedpolyelectrolyte capsules. Nano Today 2008;3:12–21.

[52] Szarpak A, Cui D, Dubreuil Fdr, De Geest BG, De Cock LJ, Picart C, et al. Designinghyaluronic acid-based layer-by-layer capsules as a carrier for intracellular drugdelivery. Biomacromolecules 2010;11:713–20.

[53] De Geest BG, Vandenbroucke RE, Guenther AM, Sukhorukov GB, Hennink WE,Sanders NN, et al. Intracellularly degradable polyelectrolyte microcapsules. AdvMater 2006;18:1005–9.

[54] Antipov AA, Sukhorukov GB, Donath E, Möhwald H. Sustained release properties ofpolyelectrolyte multilayer capsules. J Phys Chem B 2001;105:2281–4.

[55] BédardMF, De Geest BG, Skirtach AG, Möhwald H, Sukhorukov GB. Polymericmicro-capsules with light responsive properties for encapsulation and release. Adv ColloidInterface Sci 2010;158:2–14.

[56] Cabane E, Malinova V, Meier W. Synthesis of photocleavable amphiphilic block co-polymers: toward the design of photosensitive nanocarriers. Macromol Chem Phys2010;211:1847–56.

[57] Cabane E, Malinova V, Menon S, Palivan CG, Meier W. Photoresponsivepolymersomes as smart, triggerable nanocarriers. Soft Matter 2011;7:9167–76.

[58] Ghosh P, Han G, De M, Kim CK, Rotello VM. Gold nanoparticles in delivery applica-tions. Adv Drug Deliv Rev 2008;60:1307–15.

[59] Yager KG, Barrett CJ. Novel photo-switching using azobenzene functional materials. JPhotochem Photobiol A Chem 2006;182:250–61.

[60] Matsumoto M, Terrettaz S, Tachibana H. Photo-induced structural changes ofazobenzene Langmuir–Blodgett films. Adv Colloid Interface Sci 2000;87:147–64.

[61] Song X, Perlstein J, Whitten DG. Supramolecular aggregates of azobenzenephospholipids and related compounds in bilayer assemblies and othermicroheterogeneous media: structure, properties, and photoreactivity. J AmChem Soc 1997;119:9144–59.

[62] Lin Y-L, Chang H-Y, Sheng Y-J, Tsao H-K. Photoresponsive polymersomes formed byamphiphilic linear–dendritic block copolymers: generation-dependent aggregationbehavior. Macromolecules 2012;45:7143–56.

[63] Yi Q, Sukhorukov GB. UV-induced disruption of microcapsules with azobenzenegroups. Soft Matter 2014. http://dx.doi.org/10.1039/C3SM51648B.

[64] Dante S, Advincula R, Frank CW, Stroeve P. Photoisomerization of polyionic layer-by-layer films containing azobenzene. Langmuir 1999;15:193–201.

[65] Sun J, Wu T, Sun Y, Wang Z, Zhang X, Shen J, et al. Fabrication of a covalently at-tached multilayer via photolysis of layer-by-layer self-assembled films containingdiazo-resins. Chem Commun 1998:1853–4.

[66] Bédard MF, Sadasivan S, Sukhorukov GB, Skirtach A. Assembling polyelectrolytesand porphyrins into hollow capsules with laser-responsive oxidative properties. JMater Chem 2009;19:2226–33.

[67] Xu W, Choi I, Plamper FA, Synatschke CV, Müller AH, Tsukruk VV. Nondestructivelight-initiated tuning of layer-by-layer microcapsule permeability. ACS Nano2012;7:598–613.

[68] Koo HY, Lee H-J, Kim JK, San Choi W. UV-triggered encapsulation and release frompolyelectrolyte microcapsules decorated with photoacid generators. J Mater Chem2010;20:3932–7.

[69] Erokhina S, Benassi L, Bianchini P, Diaspro A, Erokhin V, Fontana M. Light-driven re-lease from polymeric microcapsules functionalized with bacteriorhodopsin. J AmChem Soc 2009;131:9800–4.

[70] Mauser T, Déjugnat C, Sukhorukov GB. Reversible pH-dependent properties of mul-tilayer microcapsules made of weak polyelectrolytes. Macromol Rapid Commun2004;25:1781–5.

[71] Shu S, Zhang X, Wu Z, Wang Z, Li C. Gradient cross-linked biodegradable poly-electrolyte nanocapsules for intracellular protein drug delivery. Biomaterials2010;31:6039–49.

[72] Yi Q, Sukhorukov GB. Externally triggered dual-function of complex microcapsules.ACS Nano 2013;7:8693–705.

[73] Kabatc J. Multicationic monomethine dyes as sensitizers in two- and three-component photoinitiating systems for multiacrylate monomers. J PhotochemPhotobiol A Chem 2010;214:74–85.

[74] Watanabe E, KawabataM, Sumiyoshi I. Near infrared polymerizable composition. USPatent 5496903, 1996.









































































































































































Documents

UV light stimulated encapsulation and release by polyelectrolyte microcapsules