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Poly(amidoamine) and Poly(propyleneimine) Dendrimers Show Distinct Binding Behaviors with Sodium Dodecyl Sulfate: Insights from SAXS and NMR Analysis Tianfu Li, Naimin Shao, Yuntao Liu, Jingjing Hu, § Yu Wang, Li Zhang, Hongli Wang, Dongfeng Chen,* ,and Yiyun Cheng* ,,China Institute of Atomic Energy, Beijing 102413, Peoples Republic of China Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200062, Peoples Republic of China § Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian 116024, Peoples Republic of China Shanghai Key Laboratory of Magnetic Resonance, Department of Physics, East China Normal University, Shanghai 200062, Peoples Republic of China * S Supporting Information ABSTRACT: We investigate the interactions of generation 3 (G3) poly- (amidoamine) (PAMAM) and G3 poly(propylenimine) (PPI) dendrimers with sodium dodecyl sulfate (SDS) in aqueous solution. Size and structure of the dendrimerSDS aggregates as a function of SDS/dendrimer molar ratio were revealed by SAXS and NMR. G3 PAMAM has a relatively open and dense-core structure, while G3 PPI with the same number of surface amine groups possesses a compact and uniform structure. Upon addition of SDS, much more SDS monomers were encapsulated in the interior of PPI rather than in PAMAM. More signicant size increase in PAMAMSDS aggregate is observed at low SDS concentrations, due to the binding of SDS on PAMAM surface and further assembly into larger supramolecular structures. Both noncooperative and cooperative binding of SDS on G3 PPI surface are observed, while only noncooperative binding is proposed on G3 PAMAM, due to its open surface and large surface group distance. The size of the PPISDS complex is larger than that of PAMAMSDS at higher SDS concentrations. Within the investigated SDS concentrations, SDS exhibits much stronger interactions with G3 PPI than with G3 PAMAM. These results provide new insights into dendrimersurfactant interactions and explain why PPI is much more cytotoxic than PAMAM. INTRODUCTION Dendrimers are promising macromolecules with well-dened tree-like spherical structures. 1,2 They comprise three main components: a central core, repeat units with branched structures, and surface functionalities. 3 Because of the unique properties like monodispersity, nanoscale size, large numbers of surface functionalities, and interior cavities, dendrimers have gained great interest in elds ranging from polymer chemistry and material chemistry to industrial and biomedical applications during the past decades. 4,5 Among these researches, the hostguest behaviors of dendrimers toward a list of guests such as drugs, dyes, surfactants, catalysts, biomacromolecules, and inorganic nanoparticles have held great scientic interest due to their key roles in the broad applications of dendrimers. 6 Surfactants are ideal candidates as guests in dendrimer-based hostguest systems due to their amphiphilic nature, charged or noncharged polar head, and nanoscale size. 711 Their complexes with dendrimers can be used as templates to guide the synthesis of nanoparticles and as vehicles of drugs or genes and show synergistic eects compared to single dendrimers and surfactants. 12,13 To date, the interactions of dendrimers and surfactants were investigated by techniques such as nuclear magnetic resonance (NMR), 6 electron paramagnetic resonance (EPR), 14 isothermal titration calorimetry (ITC), 11 electro- motive force (EMF), 11 small-angle X-ray or neutron scattering (SAXS or SANS), 11,15 uorescent spectroscopy, 16 transmission electron microscopy (TEM), 7 atomic force microscopy (AFM), 9 and quartz crystal microbalance (QCM). 17 Den- drimersurfactant interactions are mainly driven by ionic interactions or hydrophobic interactions or a combination of the two interactions. 18,19 The interactions lead to the formation of miscellaneous aggregates. 2022 In the presence of den- drimers, surfactant usually shows lower critical aggregation concentration (CAC) compared to its critical micelle Received: December 27, 2013 Revised: February 24, 2014 Published: March 7, 2014 Article pubs.acs.org/JPCB © 2014 American Chemical Society 3074 dx.doi.org/10.1021/jp412660p | J. Phys. Chem. B 2014, 118, 30743084

Poly(amidoamine) and Poly(propyleneimine) Dendrimers Show Distinct Binding Behaviors with Sodium Dodecyl Sulfate: Insights from SAXS and NMR Analysis

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Page 1: Poly(amidoamine) and Poly(propyleneimine) Dendrimers Show Distinct Binding Behaviors with Sodium Dodecyl Sulfate: Insights from SAXS and NMR Analysis

Poly(amidoamine) and Poly(propyleneimine) Dendrimers ShowDistinct Binding Behaviors with Sodium Dodecyl Sulfate: Insightsfrom SAXS and NMR AnalysisTianfu Li,† Naimin Shao,‡ Yuntao Liu,† Jingjing Hu,§ Yu Wang,† Li Zhang,† Hongli Wang,†

Dongfeng Chen,*,† and Yiyun Cheng*,‡,∥

†China Institute of Atomic Energy, Beijing 102413, People’s Republic of China‡Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200062, People’s Republicof China§Department of Bioscience and Biotechnology, Dalian University of Technology, Dalian 116024, People’s Republic of China∥Shanghai Key Laboratory of Magnetic Resonance, Department of Physics, East China Normal University, Shanghai 200062, People’sRepublic of China

*S Supporting Information

ABSTRACT: We investigate the interactions of generation 3 (G3) poly-(amidoamine) (PAMAM) and G3 poly(propylenimine) (PPI) dendrimerswith sodium dodecyl sulfate (SDS) in aqueous solution. Size and structure ofthe dendrimer−SDS aggregates as a function of SDS/dendrimer molar ratiowere revealed by SAXS and NMR. G3 PAMAM has a relatively open anddense-core structure, while G3 PPI with the same number of surface aminegroups possesses a compact and uniform structure. Upon addition of SDS,much more SDS monomers were encapsulated in the interior of PPI ratherthan in PAMAM. More significant size increase in PAMAM−SDS aggregate isobserved at low SDS concentrations, due to the binding of SDS on PAMAMsurface and further assembly into larger supramolecular structures. Bothnoncooperative and cooperative binding of SDS on G3 PPI surface areobserved, while only noncooperative binding is proposed on G3 PAMAM, dueto its open surface and large surface group distance. The size of the PPI−SDScomplex is larger than that of PAMAM−SDS at higher SDS concentrations. Within the investigated SDS concentrations, SDSexhibits much stronger interactions with G3 PPI than with G3 PAMAM. These results provide new insights into dendrimer−surfactant interactions and explain why PPI is much more cytotoxic than PAMAM.

■ INTRODUCTION

Dendrimers are promising macromolecules with well-definedtree-like spherical structures.1,2 They comprise three maincomponents: a central core, repeat units with branchedstructures, and surface functionalities.3 Because of the uniqueproperties like monodispersity, nanoscale size, large numbers ofsurface functionalities, and interior cavities, dendrimers havegained great interest in fields ranging from polymer chemistryand material chemistry to industrial and biomedical applicationsduring the past decades.4,5 Among these researches, the host−guest behaviors of dendrimers toward a list of guests such asdrugs, dyes, surfactants, catalysts, biomacromolecules, andinorganic nanoparticles have held great scientific interest dueto their key roles in the broad applications of dendrimers.6

Surfactants are ideal candidates as guests in dendrimer-basedhost−guest systems due to their amphiphilic nature, charged ornoncharged polar head, and nanoscale size.7−11 Theircomplexes with dendrimers can be used as templates to guidethe synthesis of nanoparticles and as vehicles of drugs or genes

and show synergistic effects compared to single dendrimers andsurfactants.12,13 To date, the interactions of dendrimers andsurfactants were investigated by techniques such as nuclearmagnetic resonance (NMR),6 electron paramagnetic resonance(EPR),14 isothermal titration calorimetry (ITC),11 electro-motive force (EMF),11 small-angle X-ray or neutron scattering(SAXS or SANS),11,15 fluorescent spectroscopy,16 transmissionelectron microscopy (TEM),7 atomic force microscopy(AFM),9 and quartz crystal microbalance (QCM).17 Den-drimer−surfactant interactions are mainly driven by ionicinteractions or hydrophobic interactions or a combination ofthe two interactions.18,19 The interactions lead to the formationof miscellaneous aggregates.20−22 In the presence of den-drimers, surfactant usually shows lower critical aggregationconcentration (CAC) compared to its critical micelle

Received: December 27, 2013Revised: February 24, 2014Published: March 7, 2014

Article

pubs.acs.org/JPCB

© 2014 American Chemical Society 3074 dx.doi.org/10.1021/jp412660p | J. Phys. Chem. B 2014, 118, 3074−3084

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concentration (CMC).11,23 The effect of dendrimer core,generation and surface functionality, surfactant chain length andcharge property, environmental pH condition and saltconcentration on the interaction mechanisms, the surfactantbinding capacity of dendrimers, the CAC values, and theaggregate sizes and structures were investigated.6,11

Since the pioneer reports on dendrimer synthesis in the early1980s, more than a hundred families of dendrimer weresynthesized.24,25 Among these dendrimers, poly(amidoamine)(PAMAM) and poly(propylenimine) (PPI) dendrimers are themostly studied and characterized ones which are bothsynthesized by a divergent strategy and available on themarket.3,26 PPI dendrimer has a shorter repeated unit(−CH2CH2CH2−) compared to PAMAM dendrimer(−CH2CH2COCH2CH2−), Scheme 1), thus PPI dendrimeris smaller than PAMAM with the same number of surfacefunctionality.27 Besides the size difference, the interior of a PPIdendrimer is much more hydrophobic and congested than thatof PAMAM dendrimer due to the presence of amide groups inPAMAM interior. The structural differences of PPI andPAMAM dendrimers may have interesting physicochemicalbehaviors when acting as hosts. The more hydrophobic natureof PPI dendrimer interior indicates higher capacity forhydrophobic guest loading. A recent study reported that aPPI dendrimer is much more toxic than a PAMAM dendrimerwith the same number of surface functionality.28 To reveal theexact reason behind these interesting phenomena, we need toreveal the binding behaviors of PAMAM and PPI dendrimerswith surfactants.In the current study, we investigated the binding behaviors of

generation 3 (G3) PAMAM and G3 PPI dendrimers with ananionic surfactant−sodium dodecyl sulfate (SDS). Ourdefinition of dendrimer generation is in accordance with the

generation definition initially applied for PAMAM dendrimersby Tomalia.29 Both G3 PAMAM and G3 PPI dendrimers have32 surface amine groups on the surface (Scheme 1). In previousstudies,14,18,20,21,30−32 the binding behaviors of dendrimers withsurfactants at different pH values, dendrimer generations, saltconcentrations, and solution temperatures were investigated indetail. These parameters significantly affect the interactionsbetween dendrimers and surfactants. Here, we focus on theeffect of dendrimer structure (dendrimer chemistry, interiorhydrophobicity, and surface group density) on the bindingbehaviors at native states (pH values of the dendrimer/SDSsolutions were monitored at different surfactant/dendrimermolar concentrations, and the interactions between dendrimersand SDS were measured in water without salts). Weinvestigated the solution structures of the two dendrimersand their binding behaviors with SDS by a combination ofNMR and SAXS. NMR and SAXS are powerful and sensitivetools in characterizing dendrimer−surfactant interactions.NMR provides atomic-level and molecular-level insights intothe interaction mechanisms, molecular mobility, and spatialdistances between atoms,6 while SAXS directly givesinformation on structure and size of the yielding dendrimer−surfactant aggregates.33 A combination of two techniques canprovide detailed information on interactions of SDS with thetwo dendrimers. To the best of our knowledge, this is the firstreport on the distinct binding behaviors of PAMAM and PPIdendrimers with surfactants.

■ EXPERIMENTAL SECTION

Materials. Diaminobutane (DAB)-cored and amine-termi-nated G3 PPI dendrimer with a molecular weight of 3513 Dawas purchased from Sigma-Aldrich (St. Louis, MO). Ethyl-enediamine (EDA)-cored and amine-terminated G3 PAMAM

Scheme 1. Molecular Structures of G3 PAMAM and G3 PPI Dendrimers

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dendrimer was purchased from Dendritech, Inc. (Midland, MI).SDS was purchased from Aladdin Chemistry Co., Ltd.(Shanghai, China). Deuterium oxide was purchased fromSigma-Aldrich (St. Louis, MO). G3 PAMAM dendrimer wasstored in methanol, and the solvent was distilled before use. Allother chemicals were used as received without furtherpurification.SAXS Studies. SAXS experiments were performed on the

SAXS instrument at beamline 1W2A of the Beijing SynchrotronRadiation Facility (297.0 ± 1.0 K).34 The X-ray wavelength was1.54 Å, the selected sample-to-detector distance was chose tobe 184 cm, and the corresponding wave vector Q was rangingfrom 0.02 to 0.29 Å−1. The dendrimer concentration of all thesamples was kept at 5 mg/mL, while the molar ratios of SDSand dendrimer are 0, 4, 8, 12, 16, 32, and 64. The samples wereloaded in 1 mm path length cells and measured at roomtemperature. Buffer scattering have also been measured beforeand after measuring each sample. The measured intensity hasbeen integrated to 1D I(Q) which was then normalized to themonitored transmitted beam intensity and then subtracted theaveraged buffer scattering. The reduced data were thenanalyzed by both model independent approach and modelingmethod.Model Independent Approach: Indirect Fourier Trans-

form (IFT) Analysis. The intensity I(Q) measured in a SAXSexperiment is given by the Fourier transform of the pairdistance distribution function P(r) of the particle.35,36

∫π=∞

I Q P rQr

Qrr( ) 4 ( )

sin( )d

0 (1)

The P(r) function gives direct information about the structurein real space. The function is a measure of the probability of alldistances between a pair of points within the particles weightedby the excess electron density at the points. From the function,the maximum dimension of the particle can be directlydetermined where P(r) goes to zero, and the variation in theshapes or internal structures of the particles can be easilydetected. However, due to the finite experimental range ofscattering vectors, the influence of instrumental smearingeffects, and insufficiently corrected background scattering, it isnot possible to derive P(r) by direct inverse Fouriertransformation. Nevertheless, the IFT method, first introducedby Glatter, has been well developed and can be applied tocalculate the P(r) function. In particular, we used the programGNOM by Svergun for the calculation of P(r) from the SAXSdata.36

SAXS Data Modeling. For data modeling, the theoreticalresult of a given model can be calculated and therefore fitted tothe experimental data using the nonlinear least-squares method.For the investigated system, the SAXS intensity distributionI(Q) can be given by the analytical expression37

= +I Q AP Q S Q I( ) ( ) ( ) bgd (2)

where A is the scattering amplitude which is a function of theparticle number density and its volume and average excesselectron density, P(Q) the intramolecular structure factor, S(Q)the interdendrimer structure factor, and Ibgd the background.For the intramolecular structure factor P(Q), the spherical

“core + shell” model was applied to fit the experimental datasuccessfully, noticing the spherical shape and electron densityvariations in the radial direction of the dendrimers or SDS

micelles in our investigated systems. The analytic formulationhas been developed as38

ρ ρ ρ ρ=

−+

−⎡⎣⎢

⎤⎦⎥P Q

V j QR

QR

V j QR

QR( ) scale

3 ( ) ( ) 3 ( ) ( )c c s 1 c

c

s s solv 1 s

s

2

(3)

where j1(x) = (sin x − x cos x)/ x2, Rs = Rc + T, and Vi = (4π/3)Ri

3. ρc, ρs, and ρsolv are the electron density of the core, theshell, and the solvent, respectively, Rc radius of the core, Rs

radius of the shell, and T the thickness of the shell. In reality,the dendrimer/SDS complex may not be perfectly sphericalcore−shell structured. However, because the scatteringintensity is statistically and orientationally averaged for allparticles in the measured samples, and also the low resolutionof the technique, the core−shell model serves as a good modelin fitting the SAXS data. Therefore, the quantitive modelingresults provide instructive and helpful information.At low molar ratios of SDS and dendrimer, the contribution

of the interdendrimer correlation to I(Q) is found to benegligible in our diluted samples when the Coulomb interactionbetween dendrimers can be ignored. As increasing SDSconcentration, the SDS/dendrimer complexes became effec-tively charged. Therefore, significant interparticle interferencepeak in SAXS data at low Q range was found due to the strongCoulomb interaction. The S(Q) was calculated using themethod developed by Hansen et al. and included in themodeling,39 and we used the software package developed byKline40 to conduct the modeling. The adjusted modelparameters are the effective charge, ionic strength, and volumefraction. Therefore, the charging status of the complex can bemonitored based on the modeling results.

1H NMR Studies. All the NMR spectra were acquired at298.2 ± 0.1 K on a Varian 699.804 MHz NMR spectrometer,equipped with a 5 mm standard probe. The 1H NMR spectrawere obtained with 32 scans and a 2 s relaxation delay. Thesamples were maintained at least 2 min to avoid the fluctuationof temperature before each acquisition. The concentration ofPPI dendrimer and PAMAM dendrimer for each sample is 2mg/mL. The molar ratios of SDS and dendrimer are 0.5, 1, 2, 3,4, 6, 8, 12, 16, 32, 64, and 128. Dioxane was added as aninternal standard.

Pulse Gradient Spin Echo (PGSE) NMR Studies. Theself-diffusion coefficients of dendrimer−SDS complexes weremeasured by a standard PGSE sequence on the same NMRinstrument at 298.2 ± 0.1 K. The heater and cooling unit wasswitched on to reach and stabilize the desired temperature,which avoids the influence of temperature variation on diffusionmeasurement. The time interval (Δ) between gradient pulses is100 ms and 400 ms for dioxane and dendrimer−SDScomplexes, respectively. The duration time of gradient pulses(δ) is 3 ms. The recycle time is 10 s. The pulse gradients (g)linearly increased in 16 steps to attenuate the spin-echo signal,and the maximum gradient strength is 70 G/cm. The gradientpulse was calibrated on a mixture of D2O and H2O (10% D2Oand 90% H2O) under the same experimental conditions. Thediffusion coefficients (D) of each sample were obtained byfitting the spin-echo signal and gradient strength by theequation

γ δ δ= − Δ −I I D gexp[ ( /3) ]n 02 2 2

(4)

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where In and I0 are the intensities of spin-echo signal when thesine-shaped field gradient is present and absent, respectively,and γ is the proton magnetogyric ratio (2.68 × 108 s−1 T−1).Two-Dimensional Nuclear Overhauser Spectroscopy

(2D NOESY) Studies. The 2D NOESY experiment wasconducted to confirm if the SDS molecules are encapsulatedwithin the interior pockets of PPI or PAMAM dendrimers. TheNOESY experiments for PPI−SDS and PAMAM−SDScomplexes were conducted on the same NMR instrument at298.2 ± 0.1 K using standard pulse sequences. A watersuppression pulse was added to improve signal sensitivity. 1 srelaxation delay, 146.63 ms acquisition time, a 6.5 μs 90°pulsewidth, and a 300 ms mixing time were chosen. 32 transientswere averaged for 512 × 1024 complex points. All the data wereprocessed with NMRpipe software on a Linux workstation.

■ RESULTS AND DISCUSSIONStructural Differences of G3 PPI and G3 PAMAM

Dendrimers. The SAXS data for G3 PAMAM and G3 PPIdendrimers in Figure 1 were fitted using the core−shell model.The overall radius of G3 PPI is calculated to be 15.7 Å, which ismuch smaller than that of G3 PAMAM (23.5 Å, Table 1). The

fitting results suggest that G3 PPI dendrimer has a uniformdensity profile throughout the dendrimer (shell thickness iszero), while G3 PAMAM has a shell thickness around 11.1 Åwith electron density closer to that of solvent water. The core−shell structure of PAMAM dendrimer is in accordance withearlier studies.41 Similar results are observed from the pairdistance distribution functions P(r) for both dendrimers. Asshown in Figure 2, compared to the P(r) calculated forhomogeneous spheres of the same size and molecular weight,the P(r) for G3 PAMAM and G3 PPI shift to smaller distances.In addition, the P(r) for G3 PAMAM has smaller values at largedistances than that of homogeneous sphere. This is due to thelower branching density at the surface region of G3 PAMAM;in other words, G3 PAMAM dendrimer has a fuzzier surface. Incomparison, the P(r) for G3 PPI is rather close to that ofhomogeneous sphere at large distances, indicating the

homogeneous branching density distribution throughout thedendrimer.The conformation of dendrimer in solution has been

extensively studied both theoretically and experimentally, andthe dense-core model, rather than the dense-shell model, is bynow accepted as the correct one.42,43 Usually, a structuretransition from an open surface to a closed and congestedsurface for PAMAM dendrimers is observed above generation 4or 4.5.44 The fuzzier surface and core−shell structure of G3PAMAM dendrimer in our SAXS analysis is in accordance withthis rule. The dendrimer structure also depends on its repeatedunit and surface charge. Considering the shorter and morehydrophobic repeated unit of PPI compared to PAMAMdendrimer, it is not hard to understand that G3 PPI has a ratheruniform branch density distribution. In contrast, the longer andless hydrophobic repeated unit of G3 PAMAM provides morefreedom for branch back-folding or turning and strongerinteractions with solvent water. Therefore, a fuzzy surfacesphere with flexible branching unit, less hydrophobic interiorand lower surface group density for G3 PAMAM compared torather homogeneous sphere with stiff branching unit, hydro-phobic interior, and higher surface group density for G3 PPIcan be concluded (Table 1). The structural differences motivateus to investigate the binding behaviors of G3 PAMAM and G3PPI dendrimers with surfactants.

Figure 1. SAXS data for G3 PAMAM and G3 PPI dendrimers fitted using a core−shell model.

Table 1. Structures of G3 PAMAM and G3 PPI Dendrimers

dendrimeroverall radius(Å) (SAXS)

surfacegroupnumber

surface grouparea (Å2)

surface groupdistance (Å)

G3PAMAM

23.5 ± 0.2 32 217 14.7 ± 0.2

G3 PPI 15.7 ± 0.4 32 96.8 9.8 ± 0.3

Figure 2. Pair distance distribution function P(r) determined by IFTfrom the SAXS data for G3 PAMAM and G3 PPI dendrimers. Thefunctions calculated from homogeneous spheres with the same sizeand molecular weight are also given (the same SAXS intensity at Q = 0determined by IFT, which is proportional to the integrated electrondensity over the whole dendrimer volume).

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Binding Behaviors of G3 PAMAM and G3 PPIDendrimers with SDS. As shown in Figures 3 and 4, G3PAMAM and G3 PPI show distinct binding behaviors with SDSwithin the SDS/dendrimer molar ratio of 0−4. At a SDS/dendrimer molar ratio of 0.5, the relative diffusion coefficient ofSDS in G3 PAMAM−SDS complex determined by PGSENMR is about 3 times larger than that in the G3 PPI−SDScomplex. The diffusion coefficient of SDS is similar to that ofG3 PPI in the G3 PPI−SDS complex, suggesting that SDS istightly bound with the PPI dendrimer. With increasing SDS/dendrimer molar ratios (0−4), the relative diffusion coefficientof G3 PPI dendrimer increases while that of G3 PAMAMdecreases. This phenomenon can be explained by theencapsulation of SDS molecules within G3 PPI dendrimerand the ionic binding of SDS molecules on the surface of G3PAMAM dendrimer (Scheme 2). Hydrophobic interactionsbetween the aliphatic chain of SDS and hydrophobic interior ofG3 PPI dendrimer lead to a shrunk structure of the complexcompared to free G3 PPI dendrimer.22 On the other hand, SDSmolecules binding on the surface of G3 PAMAM dendrimercauses increased dendrimer size with increasing SDS/dendrimer molar ratios. This model well explains why SDS inthe G3 PPI−SDS complex has a similar diffusion coefficientwith G3 PPI (slow exchange of free and bound state) but showsmuch higher diffusion coefficient in the G3 PAMAM−SDScomplex than the dendrimer (fast exchange of free and boundstate).We further conducted a 1H−1H 2D NOESY experiment to

confirm the inclusion structure of G3 PPI−SDS com-plexes.45−47 As shown in Figure 5a, strong NOE interactionsbetween the protons H3 of SDS protons and G3 PPI protonsand medium interactions between protons (H1 and H4) of SDSand dendrimer protons are observed, indicating encapsulationof SDS molecules within the interior pockets of G3 PPIdendrimer.19 Since peak HA of G3 PPI is overlapped with peakH2 of SDS, the cross-peaks at related regions are not discussed.However, for the G3 PAMAM−SDS complex, only mediumNOE interactions between protons H3 of SDS and dendrimerprotons (Ha−d) are observed in Figure 5b. Considering that G3PAMAM has a larger molecular weight (6900 Da) than G3 PPI(3513 Da), the weaker NOE cross-peaks for the G3 PAMAM−SDS complex in Figure 5 at the same mixing time suggest that

Figure 3. Diffusion coefficients of G3 PAMAM and G3 PPIdendrimers relative to those of dioxane in the presence of differentamounts of SDS. The molar ratio of SDS and dendrimer ranges from0.5 to 128. Dioxane was used as an internal standard to rule out theinfluence of solvent viscosity on the diffusion coefficients. The protonson PAMAM (Ha−d) and PPI (HA−C) dendrimers in this study areassigned according to reference 28.

Figure 4. Diffusion coefficients of SDS relative to those of dioxane inG3 PAMAM−SDS and G3 PPI−SDS complexes. The molar ratio ofSDS and dendrimer ranges from 0.5 to 128. The protons on SDS(H1−4) in this study are assigned according to reference 28.

Scheme 2. Binding of SDS Molecules in the Interior and on the Surface of G3 PPI (a) and G3 PAMAM (b) Dendrimers

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much fewer SDS molecules are encapsulated within the G3PAMAM dendrimer. This distinct encapsulation behavior ismainly due to the hydrophobic nature of the G3 PPI interiorand the relative polar microenvironment of the G3 PAMAMinterior.At SDS/dendrimer molar ratios of 4−12, the diffusion

coefficient of G3 PPI also significantly decreases (Figure 3).This is due to the saturation of SDS encapsulation within PPIdendrimer interior and binding of SDS molecules on its surface.During this period, a SDS bilayer structure is proposed to formon the surface of G3 PPI dendrimer. This is evident from the1H NMR spectra of G3 PPI−SDS complexes in Figure 6a. The

methylene protons (HC) located on the dendrimer surfaceexhibit a downfield shift due to the ionic bindings of SDSmolecules.27 Especially at SDS/G3 PPI molar ratios of 6 and 8,three independent peaks for HC were observed. Thisphenomenon can be explained by a coexistence of non-cooperative and cooperative binding SDS on G3 PPI surface,which is already discussed in our previous study for G4PAMAM−SDS complexes.22 In comparison, only noncoop-erative binding of SDS on G3 PAMAM dendrimer is observedin Figure 6b. Tomalia et al. demonstrated that the non-cooperative or cooperative binding of surfactants on dendrimersurface depends much on dendrimer generation.44 Surfactantinteracts with low generation dendrimers (G ≤ 3.5) vianoncooperative ionic bindings but binds with high generationdendrimers (G ≥ 4.5) through cooperative bindings. Thisdistinct behavior was attributed to the transition of dendrimermorphology from an open structure of low generationdendrimers to a congested structure of high generation ones.High surface charge density of the latter generations leads tothe observed cooperative binding. Most recently, Wagner andLi found that the cooperative binding strength increasesquadratically with the polyelectrolyte’s charge density and inproportion to the surfactant’s hydrophobicity in a polyelec-trolyte−surfactant system.48 As revealed in our SAXS analysis,G3 PPI dendrimer has dense surface groups while G3 PAMAMdendrimer has a fuzzy and open surface. Considering both

Figure 5. 2D NOESY spectra of G3 PPI−SDS (a) and G3 PAMAM−SDS (b) complexes at a SDS/dendrimer molar ratio of 4. The mixingtime for both spectra is 300 ms.

Figure 6. 1H NMR of G3 PPI (a) and G3 PAMAM (b) dendrimerstitrated with different SDS/dendrimer molar ratios. The red arrows in(a) represent the coexistence of non-cooperative and cooperativebinding SDS on G3 PPI dendrimer.

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dendrimer has 32 surface amine groups and G3 PPI is smallerthan G3 PAMAM, the group distance on G3 PPI dendrimer ismuch smaller than that on G3 PAMAM dendrimer (Table 1).The differences in surface group density and dendrimerstructure of the two dendrimers well explain the distinctbinding behavior of SDS on G3 PPI and G3 PAMAM surfaceduring this period.At SDS/dendrimer molar ratios above 12, G3 PPI and SDS

form a larger aggregate than the G3 PAMAM−SDS complex.During this period, SDS forms micelles in the interactingsolution. G3 PAMAM dendrimer interacts with these SDSmicelles in a fast-exchange fashion. In comparison, the SDSbilayer formed on G3 PPI dendrimer by cooperative bindingsconnects two PPI dendrimers, forming a dumbbell-likestructure. Such a dumbbell structure is proposed by Ottavianiet al. using EPR and can explain why the G3 PPI−SDS complexis larger than the G3 PAMAM complex at high SDSconcentrations.20,21

The interactions of SDS with G3 PAMAM and G3 PPIdendrimer are further investigated by SAXS. The SAXS data fordendrimer−SDS complexes at different molar ratios wereanalyzed by the IFT method. As shown in Figures 7 and 8,significant increases in the scattering intensity upon addition ofSDS are observed, indicating the binding or association of SDS

molecules to both dendrimers. The maximum distance in theaggregates, as determined from the P(r), is much larger thanthat of dendrimer in the absence of SDS. At high SDS/dendrimer molar ratios, P(r) functions for both dendrimercomplexes showed similar behavior to that of pure SDS micelle,indicating the formation of SDS micelles. The appearance ofnegative values at the middle distances are due to the wellassembled SDS which has lower electron density of thehydrophobic tail and higher electron density of the hydrophilichead than solvent water. It is interesting to note that, for G3PPI dendrimer, negative values of P(r) can be found at allmeasured molar ratios, while for the G3 PAMAM dendrimer,negative P(r) values only start to appear until molar ratioreaches 64. This means that PPI has more significant effect onthe assembly of SDS into micelles. This phenomenon is inaccordance with the results from NMR analysis that a SDSbilayer structure is formed on the surface of PPI dendrimer viacooperative bindings.In Figures 7 and 8, it is also found that at high molar ratios of

SDS and dendrimer the theoretical results do not agree withexperimental data in the low Q range which is due to theignorance of the interparticle structure factor S(Q) in the IFTanalysis. To accounting for the S(Q), we have also performedthe data modeling analysis (Figure 9 and Table S1). The SDS/dendrimers complexes were effectively charged at high molarratios due to the formation of SDS micelles. The variations of

Figure 7. Top: SAXS data and IFT analysis for G3 PAMAM−SDS atdifferent molar ratios. The dots are the experimental SAXS data, andthe solid lines are the fitted results. Bottom: P(r) functions for the G3PAMAM−SDS complexes determined by IFT analysis.

Figure 8. Top: SAXS data and IFT analysis for G3 PPI−SDS atdifferent molar ratios. Bottom: P(r) functions for the G3 PPI−SDScomplexes determined by IFT analysis.

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the overall aggregate size for both dendrimers at different SDS/dendrimer molar ratios are shown in Figure 10. For G3

PAMAM dendrimer, the maximum distance and overallaggregate size increases to very large values (>80 Å) at SDS/dendrimer molar ratios of 4 and 8, indicating formation of largeaggregates. During this molar ratio range, SDS monomer bindswith G3 PAMAM dendrimer surface and several G3 PAMAMdendrimers may associate with each other via hydrophobicinteractions between the bound SDS molecules, yielding alarger aggregate structure (Scheme 3). Further addition of SDSmolecules disassembles this aggregate structure and the finalsize of the complex decreases to 55 Å at SDS/dendrimer molarratios above 12. This is because SDS form micelles on thedendrimer surface and the aggregates carrying net negativecharges repulse with each other, preventing the formation ofaggregates. Interestingly, this assembly and disassembly processis not observed in the diffusion coefficient analysis in Figure 3,in which the size of dendrimer aggregate increases withincreasing SDS/dendrimer molar ratios and finally achieves aconstant size at molar ratios above 64. This is because weanalyze the diffusion coefficient of dendrimer or SDS in PGSE

Figure 9. Fitting the SAXS data of G3 PAMAM−SDS (a) and G3 PPI−SDS (b) complexes using a core−shell model.

Figure 10. Size variations of the dendrimer−SDS complexes atdifferent SDS/dendrimer molar ratios based on the SAXS datamodeling.

Scheme 3. SDS Molecules Bound on the Surface of G3 PAMAM Dendrimer Causes the Formation of Larger Aggregates at aSDS/G3 PAMAM Molar Ratio of 4

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NMR but the whole aggregate size in the SAXS analysis. TheG3 PAMAM dendrimer−surfactant aggregate is formed bynoncooperative interactions and the SDS molecules are in a fastexchange of free and bound state. In this case, the dimension ofthe loosely bounded aggregates is not simply inverselyproportional to the diffusion coefficient. And at high molarratios, the binding of more SDS and the appearance ofinterparticle repulsion would further suppress the diffusion ofdendrimers. For G3 PPI dendrimer, the encapsulation of SDSmonomers within the dendrimer interior pockets at low SDS/dendrimer ratios is followed by the cooperative binding of SDSon dendrimer surface at high SDS/dendrimer ratios. Therefore,no large aggregate structure was examined in the SAXSmeasurements. The size of the G3 PPI−SDS complex graduallyincreases to a stable value of 60 Å, which is larger than the sizeof G3 PAMAM−SDS complex. This result is in accordancewith the diffusion coefficient variations of both dendrimers inthe presence of SDS in Figure 3.Within the investigated SDS/dendrimer molar ratio (0−

128), SDS interacts much more strongly with G3 PPIdendrimer than with G3 PAMAM dendrimer. This is evidentin the PGSE NMR analysis in Figure 4. At all SDS/dendrimermolar ratios, SDS in the G3 PPI−SDS system shows muchlower diffusion coefficients than that in the G3 PAMAM−SDSsystem. This is attributed to the encapsulations of SDS withinG3 PPI dendrimer at low SDS/dendrimer molar ratios andbinding of SDS on its surface via cooperative interactions athigher ratios. The distinct binding behaviors of SDS in theinterior and on the surface of both dendrimers are notattributed to different pH values of the dendrimer−SDSmixture solutions due to the following reasons. (1) The pKavalues of tertiary amines in the interior of PAMAM and PPIdendrimers are around 6.0,49,50 and the pH values of all thecomplex solutions are above 8.45 (Table S2 in the SupportingInformation). The tertiary amine groups in the interior of bothdendrimers are not protonated during the addition of SDSmolecules. In this case, the stronger binding of SDS within PPIdendrimer interior is due to the more hydrophobic nature ofPPI dendrimer interior rather than different protonation statesof the tertiary amine groups. (2) The pH values of G3 PPI/SDS solutions (9.88−12.07) are higher than that of G3PAMAM/SDS solutions (8.45−10.98) at equal SDS/den-drimer molar ratios (Table S2). In this case, a smaller percentof surface amine groups on G3 PPI dendrimers are protonatedthan on G3 PAMAM dendrimers during the addition of SDSmolecules (pKa values of the surface amine groups of PAMAMand PPI dendrimers are around 10.0).51,52 Therefore, thestronger interactions of SDS on PPI dendrimer surface than onPAMAM dendrimer is mainly due to distinct structures of bothdendrimers as revealed by SAXS analysis rather than differentpH values or protonation states. At high SDS/dendrimer molarratios (32:1 to 128:1), the pH values of PPI/SDS solutions arearound 12.0, and most of the surface amine groups are notprotonated. The cooperative interactions between SDS and thePPI dendrimer surface should be ion-dipole interactions ratherthan ionic interactions during this period. The strongerinteraction of surfactants such as SDS with G3 PPI than withG3 PAMAM provides insights into the cytotoxicity profiles ofboth dendrimers. Phospholipids such as dimyristoylphosphati-dylcholine (DMPC) are also surfactants with hydrophobic tailsand a hydrophilic and charged head.53,54 Thus, G3 PPIdendrimer should interact strongly with these biosurfactants,which are main components of cell membrane. The strong

interactions between PPI dendrimer and cell membrane mayinduce pore formation on the cell membrane and followed byleakage of intracellular proteins.55 Such a result well explainswhy G3 PPI dendrimer is much more toxic (>50-fold) than G3PAMAM dendrimer.28 As demonstrated by previous studies,the interactions between dendrimers and surfactants dependmuch on dendrimer generation, dendrimer surface function-ality, surfactant property (i.e., length and number of hydro-phobic tails and charge property of hydrophilic head), solutionpH value, ionic strength, and temperature.56 In future studies,we will compare the binding behaviors of PAMAM and PPIdendrimers of different generations with biosurfactants such asDMPC to investigate the exact reason behind the distincttoxicity profiles of both dendrimers and the above parameterswill be considered.

■ CONCLUSIONS

Dendrimer−surfactant interactions have held great scientificinterest because of synergistic effect of the dendrimer−surfactant complex and their potentials for broad applicationsin industry, pharmaceutical sciences, and biological systems.6

Although many studies have investigated such interactions inaqueous solutions and at interface of phases during the past twodecades, no report on the behaviors of PAMAM dendrimerversus PPI dendrimer in their interactions with surfactants isavailable. The comparison of PAMAM and PPI dendrimers canprovide insights into their distinct behaviors in biologicalsystems such as cytotoxicity and cellular uptake process. In thisstudy, we investigated the structure differences betweenPAMAM and PPI dendrimers and compared their bindingbehaviors with an anionic surfactant by a combination of NMRand SAXS analysis. G3 PAMAM dendrimer shows a relativelyloose, open, and dense-core structure and G3 PPI has acompact, closed, and uniform one. At low SDS/dendrimermolar ratios, G3 PPI mainly encapsulates SDS monomerswithin its interior pockets while G3 PAMAM interacts withSDS molecules on its surface by noncooperative interactions(supported by PGSE and NOESY). This process continuesuntil the SDS encapsulation within G3 PPI is saturated. ThenSDS also binds on G3 PPI surface via noncooperative ionicinteractions (supported by PGSE) and followed by a gradualtransition from a noncooperative binding to a cooperative oneat higher SDS/G3 PPI molar ratios (supported by 1H NMRtitration). G3 PAMAM dendrimer forms larger aggregates withSDS at low SDS/dendrimer molar ratios (4 or 8) and followedby disassembly of the aggregate at higher ratios (supported bySAXS analysis). The G3 PAMAM−SDS complex size is largerthan the size of the G3 PPI−SDS complex at low SDS/dendrimer molar ratios; as the binding proceeds, a reverse trendis observed at high molar ratios (supported by both PGSENMR and SAXS). At all SDS/dendrimer molar ratios, SDSinteracts much more strongly with G3 PPI rather than with G3PAMAM. These binding behaviors are due to distinct interiorcharacters and surface structures of G3 PAMAM and G3 PPIdendrimers. Such results are helpful for us to understand thedistinct toxicity profiles of PAMAM and PPI dendrimers andprovide new insights into the design of biocompatibledendrimers for drug and gene delivery.

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■ ASSOCIATED CONTENT

*S Supporting InformationFurther information on SAXS analysis and pH values of thedendrimer/SDS complex solutions. This material is availablefree of charge via the Internet at http://pubs.acs.org.

■ AUTHOR INFORMATION

Corresponding Authors*E-mail [email protected] (D.C.).*E-mail [email protected] (Y.C.).

Author ContributionsT.L. and N.S. contributed equally to this manuscript.

NotesThe authors declare no competing financial interest.

■ ACKNOWLEDGMENTSWe gratefully acknowledge the support of the BSRF inproviding the SAXS research facility and thank Dr. GuangMo, Prof. Zhihong Li, and Prof. Zhonghua Wu for their kindhelp in conducting the SAXS measurement. We thank theSpecialized Research Fund for the Doctoral Program of HigherEducation (No. 20120076110021), the National ScienceFoundation of China (No. 11005159, No.595 1105232), andthe “973 program” (No. 2010CB833105) for financial supportof this work.

■ REFERENCES(1) Tomalia, D. A. Interview: An Architectural Journey: From Trees,Dendrons/Dendrimers to Nanomedicine. Nanomedicine 2012, 7, 953−956.(2) Tomalia, D. A. Dendritic Effects: Dependency of DendriticNano-Periodic Property Patterns on Critical Nanoscale DesignParameters (CNDPs). New J. Chem. 2012, 36, 264−281.(3) Tomalia, D. A. Birth of a New Macromolecular Architecture:Dendrimers as Quantized Building Blocks for Nanoscale SyntheticPolymer Chemistry. Prog. Polym. Sci. 2005, 30, 294−324.(4) Menjoge, A. R.; Kannan, R. M.; Tomalia, D. A. Dendrimer-BasedDrug and Imaging Conjugates: Design Considerations for Nano-medical Applications. Drug Discovery Today 2010, 15, 171−185.(5) Cheng, Y.; Zhao, L.; Li, Y.; Xu, T. Design of BiocompatibleDendrimers for Cancer Diagnosis and Therapy: Current Status andFuture Perspectives. Chem. Soc. Rev. 2011, 40, 2673−2703.(6) Hu, J.; Xu, T.; Cheng, Y. NMR Insights into Dendrimer-BasedHost-Guest Systems. Chem. Rev. 2012, 112, 3856−3891.(7) Kelly, C. V.; Liroff, M. G.; Triplett, L. D.; Leroueil, P. R.; Mullen,D. G.; Wallace, J. M.; Meshinchi, S.; Baker, J. R., Jr.; Orr, B. G.;Banaszak Holl, M. M. Stoichiometry and Structure of Poly-(amidoamine) Dendrimer-Lipid Complexes. ACS Nano 2009, 3,1886−1896.(8) Smith, P. E.; Brender, J. R.; Durr, U. H.; Xu, J.; Mullen, D. G.;Banaszak Holl, M. M.; Ramamoorthy, A. Solid-State NMR Reveals theHydrophobic-Core Location of Poly(amidoamine) Dendrimers inBiomembranes. J. Am. Chem. Soc. 2010, 132, 8087−8097.(9) Lind, T. K.; Zielinska, P.; Wacklin, H. P.; Urban czyk-Lipkowska,Z.; Cardenas, M. Continuous Flow Atomic Force Microscopy ImagingReveals Fluidity and Time Dependent Interactions of AntimicrobialDendrimer with Model Lipid Membranes. ACS Nano 2014, 8, 396−408.(10) Wu, Q.; Cheng, Y.; Hu, J.; Zhao, L.; Xu, T. Insights into theInteractions between Dendrimers and Bioactive Surfactants: 3. Size-Dependent and Hydrophobic Property-Dependent Encapsulation ofBile Salts. J. Phys. Chem. B 2009, 113, 12934−12943.(11) Tam, K. C.; Wyn-Jones, E. Insights on Polymer SurfactantComplex Structures during the Binding of Surfactants to Polymers as

Measured by Equilibrium and Structural Techniques. Chem. Soc. Rev.2006, 35, 693−709.(12) Cheng, Y.; Wu, Q.; Li, Y.; Hu, J.; Xu, T. New Insights into theInteractions between Dendrimers and Surfactants: 2. Design of NewDrug Formulations Based on Dendrimer-Surfactant Aggregates. J.Phys. Chem. B 2009, 113, 8339−8346.(13) Donners, J. J.; Nolte, R. J.; Sommerdijk, N. A. Dendrimer-BasedHydroxyapatite Composites with Remarkable Materials Properties.Adv. Mater. 2003, 15, 313−316.(14) Ottaviani, M. F.; Favuzza, P.; Sacchi, B.; Turro, N. J.; Jockusch,S.; Tomalia, D. A. Interactions between Starburst Dendrimers andMixed DMPC/DMPA-Na Vesicles Studied by the Spin Label and theSpin Probe Techniques, Supported by Transmission ElectronMicroscopy. Langmuir 2002, 18, 2347−2357.(15) Li, X.; Imae, T.; Leisner, D.; Lopez-Quintela, M. A. LamellarStructures of Anionic Poly(amido amine) Dendrimers with OppositelyCharged Didodecyldimethylammonium Bromide. J. Phys. Chem. B2002, 106, 12170−12177.(16) Hu, C.; Yang, H.; Li, R.; Wu, X.; Wang, J. Aggregation Behaviorof Amphiphilic Dendritic Block Copolymer with Butanediyl-α,ω-bis(tetradecyldimethylammonium bromide) in Aqueous Solution. J.Chem. Eng. Data 2010, 55, 4221−4226.(17) Yanez Arteta, M.; Eltes, F.; Campbell, R. A.; Nylander, T.Interactions of PAMAM Dendrimers with SDS at the Solid-LiquidInterface. Langmuir 2013, 29, 5817−5831.(18) Wang, C.; Wyn-Jones, E.; Sidhu, J.; Tam, K. C. SupramolecularComplex Induced by the Binding of Sodium Dodecyl Sulfate toPAMAM Dendrimers. Langmuir 2007, 23, 1635−1639.(19) Cheng, Y.; Li, Y.; Wu, Q.; Xu, T. New Insights into theInteractions between Dendrimers and Surfactants by Two Dimen-sional NOE NMR Spectroscopy. J. Phys. Chem. B 2008, 112, 12674−12680.(20) Ottaviani, M. F.; Turro, N. J.; Jockusch, S.; Tomalia, D. A.Aggregational Process of the Positively Charged Surfactants CTACand CAT16 in the Presence of Starburst Dendrimers: An ElectronParamagnetic Resonance Spectroscopic Study. Colloids Surf., A 1996,115, 9−21.(21) Ottaviani, M. F.; Andechaga, P.; Turro, N. J.; Tomalia, D. A.Model for the Interactions between Anionic Dendrimers and CationicSurfactants by Means of the Spin Probe Method. J. Phys. Chem. B1997, 101, 6057−6065.(22) Fang, M.; Cheng, Y.; Zhang, J.; Wu, Q.; Hu, J.; Zhao, L.; Xu, T.New Insights into Interactions between Dendrimers and Surfactants. 4.Fast-Exchange/Slow-Exchange Transitions in the Structure ofDendrimer-Surfactant Aggregates. J. Phys. Chem. B 2010, 114,6048−6055.(23) Sidhu, J.; Bloor, D.; Couderc-Azouani, S.; Penfold, J.;Holzwarth, J.; Wyn-Jones, E. Interactions of Poly(amidoamine)Dendrimers with the Surfactants SDS, DTAB, and C12EO6: AnEquilibrium and Structural Study Using a SDS Selective Electrode,Isothermal Titration Calorimetry, and Small Angle Neutron Scattering.Langmuir 2004, 20, 9320−9328.(24) Tomalia, D.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin,S.; Roeck, J.; Ryder, J.; Smith, P. A New Class of Polymers: Starburst-Dendritic Macromolecules. Polym. J. 1985, 17, 117−132.(25) Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K. Micelles.Part 1. Cascade Molecules: A New Approach to Micelles. A [27]-arborol. J. Org. Chem. 1985, 50, 2003−2004.(26) Helms, B.; Meijer, E. W. Dendrimers at Work. Science 2006,313, 929−930.(27) Wang, M.; Gong, X.; Hu, J.; Yu, Y.; Chen, Q.; Cheng, Y.Understanding the Binding Interactions between Dendrimer and 18Common Amino Acids by NMR Techniques. J. Phys. Chem. B 2011,115, 12728−12735.(28) Shao, N.; Su, Y.; Hu, J.; Zhang, J.; Zhang, H.; Cheng, Y.Comparison of Generation 3 Polyamidoamine Dendrimer andGeneration 4 Polypropylenimine Dendrimer on Drug Loading,Complex Structure, Release Behavior, and Cytotoxicity. Int. J.Nanomed. 2011, 6, 3361−3372.

The Journal of Physical Chemistry B Article

dx.doi.org/10.1021/jp412660p | J. Phys. Chem. B 2014, 118, 3074−30843083

Page 11: Poly(amidoamine) and Poly(propyleneimine) Dendrimers Show Distinct Binding Behaviors with Sodium Dodecyl Sulfate: Insights from SAXS and NMR Analysis

(29) Mark, J. E. Polymer Data Handbook; Oxford University Press:New York, 2009.(30) Ottaviani, M.; Daddi, R.; Brustolon, M.; Turro, N.; Tomalia, D.Interaction between Starburst Dendrimers and SDS micelles Studiedby Continuous-Wave and Pulsed Electron Spin Resonances. Appl.Magn. Reson. 1997, 13, 347−363.(31) Watkins, D. M.; Sayed-Sweet, Y.; Klimash, J. W.; Turro, N. J.;Tomalia, D. A. Dendrimers with Hydrophobic Cores and theFormation of Supramolecular Dendrimer-Surfactant Assemblies.Langmuir 1997, 13, 3136−3141.(32) Ottaviani, M. F.; Cossu, E.; Turro, N. J.; Tomalia, D. A.Characterization of Starburst Dendrimers by Electron ParamagneticResonance. 2. Positively Charged Nitroxide Radicals of Variable ChainLength Used as Spin Probes. J. Am. Chem. Soc. 1995, 117, 4387−4398.(33) Rambo, R. P.; Tainer, J. A. Super-Resolution in Solution X-RayScattering and Its Applications to Structural Systems Biology. Annu.Rev. Biophys. 2013, 42, 415−441.(34) Li, Z.; Wu, Z.; Mo, G.; Xing, X.; Liu, P. A Small-Angle X-RayScattering Station at Beijing Synchrotron Radiation Facility. Instrum.Sci. Technol. 2014, 42, 128−141.(35) Glatter, O. A New Method for the Evaluation of Small-AngleScattering Data. J. Appl. Crystallogr. 1977, 10, 415−421.(36) Svergun, D. Determination of the Regularization Parameter inIndirect-Transform Methods Using Perceptual Criteria. J. Appl.Crystallogr. 1992, 25, 495−503.(37) Chen, S. H. Small Angle Neutron Scattering Studies of theStructure and Interaction in Micellar and Microemulsion Systems.Annu. Rev. Phys. Chem. 1986, 37, 351−399.(38) Guinier, A.; Fournet, G.; Walker, C. B.; Yudowitch, K. L. Small-Angle Scattering of X-Rays; Wiley: New York, 1955; Vol. 14.(39) Hansen, J.-P.; Hayter, J. B. A Rescaled MSA Structure Factor forDilute Charged Colloidal Dispersions. Mol. Phys. 1982, 46, 651−656.(40) Kline, S. R. Reduction and Analysis of SANS and USANS DataUsing IGOR Pro. J. Appl. Crystallogr. 2006, 39, 895−900.(41) Rathgeber, S.; Monkenbusch, M.; Kreitschmann, M.; Urban, V.;Brulet, A. Dynamics of Star-Burst Dendrimers in Solution in Relationto Their Structural Properties. J. Chem. Phys. 2002, 117, 4047−4062.(42) Likos, C. N. Soft Matter with Soft Particles. Soft Matter 2006, 2,478−498.(43) Chen, W. R.; Porcar, L.; Liu, Y.; Butler, P. D.; Magid, L. J. SmallAngle Neutron Scattering Studies of the Counterion Effects on theMolecular Conformation and Structure of Charged G4 PAMAMDendrimers in Aqueous Solutions. Macromolecules 2007, 40, 5887−5898.(44) Caminati, G.; Turro, N. J.; Tomalia, D. A. PhotophysicalInvestigation of Starburst Dendrimers and Their Interactions withAnionic and Cationic Surfactants. J. Am. Chem. Soc. 1990, 112, 8515−8522.(45) Zhao, L.; Wu, Q.; Cheng, Y.; Zhang, J.; Wu, J.; Xu, T. High-Throughput Screening of Dendrimer-Binding Drugs. J. Am. Chem. Soc.2010, 132, 13182−13184.(46) Yang, K.; Weng, L.; Cheng, Y.; Zhang, H.; Zhang, J.; Wu, Q.;Xu, T. Host-Guest Chemistry of Dendrimer-Drug Complexes. 6. FullyAcetylated Dendrimers as Biocompatible Drug Vehicles UsingDexamethasone 21-Phosphate as a Model Drug. J. Phys. Chem. B2011, 115, 2185−2195.(47) Feng, X.; Cheng, Y.; Wu, Q.; Zhang, J.; Xu, T. Stimuli Responseof Cystamine-Core Dendrimer Revealed by Diffusion and NOE NMRStudies. J. Phys. Chem. B 2011, 115, 3777−3783.(48) Li, D.; Wagner, N. J. Universal Binding Behavior for Ionic AlkylSurfactants with Oppositely Charged Polyelectrolytes. J. Am. Chem.Soc. 2013, 135, 17547−17555.(49) Jin, G.-w.; Koo, H.; Nam, K.; Kim, H.; Lee, S.; Park, J.-S.; Lee, Y.PAMAM Dendrimer with a 1, 2-Diaminoethane Surface FacilitatesEndosomal Escape for Enhanced pDNA Delivery. Polymer 2011, 52,339−346.(50) Kabanov, V.; Zezin, A.; Rogacheva, V.; Gulyaeva, Z. G.;Zansochova, M.; Joosten, J.; Brackman, J. Polyelectrolyte Behavior of

Astramol Poly(propyleneimine) Dendrimers.Macromolecules 1998, 31,5142−5144.(51) Kannaiyan, D.; Imae, T. pH-Dependent Encapsulation ofPyrene in PPI-Core: PAMAM-Shell Dendrimers. Langmuir 2009, 25,5282−5285.(52) D’Emanuele, A.; Attwood, D. Dendrimer-Drug Interactions.Adv. Drug Delivery Rev. 2005, 57, 2147−2162.(53) Puri, A.; Blumenthal, R. Polymeric Lipid Assemblies as NovelTheranostic Tools. Acc. Chem. Res. 2011, 44, 1071−1079.(54) Muckom, R. J.; Stanzione, F.; Gandour, R. D.; Sum, A. K.Dendritic Amphiphiles Strongly Affect the Biophysical Properties ofDPPC Bilayer Membranes. J. Phys. Chem. B 2013, 117, 1810−1818.(55) Hong, S.; Bielinska, A. U.; Mecke, A.; Keszler, B.; Beals, J. L.;Shi, X.; Balogh, L.; Orr, B. G.; Baker, J. R.; Banaszak Holl, M. M.Interaction of Poly(amidoamine) Dendrimers with Supported LipidBilayers and Cells: Hole Formation and the Relation to Transport.Bioconjugate Chem. 2004, 15, 774−782.(56) Cheng, Y.; Zhao, L.; Li, T. Dendrimer-Surfactant Interactions.Soft Matter 2014, DOI: 10.1039/C3SM53180E.

The Journal of Physical Chemistry B Article

dx.doi.org/10.1021/jp412660p | J. Phys. Chem. B 2014, 118, 3074−30843084