Nanostructured Materials for Medical and Biological Applications (CREST – NSF Award Nº 1345156)

Oscar Perales, Madeline Torres, Carlos Rinaldi, Eduardo J. Juan, Maribella Domenech, Magda Latorre, Félix Román

University of Puerto Rico – Mayagüez, University of Florida Abstract: This interdisciplinary research group (IRG) of the University of Puerto Rico – Mayagüez (UPRM) Nanotechnology Center seeks to develop new nanoscaled materials for cancer therapy assisted by the application of magnetic fields and specialized light sources. Their toxicity and transport will be assessed using model human cancer cell lines and other appropriate models. The final goal of this IRG is to create non-invasive therapeutics for treatment of patients suffering from diverse forms of cancer.

Optimization of the Thermal Chemopotentiation of Anticancer Drugs by Magnetic Fluid Hyperthermia for Cancer Treatment

Toxic Metal-Free Quantum Dots For 2-Photons Photodynamic Therapy for Energy-Driven Cancer Therapy Applications

(a, b) HRTEM images of 5nm and 7nm ZnO QDs synthesized by the polyol route; (c) The enhancement of the 525nm emission intensity from the sensor green kit by prolonging UV irradiation times and higher concentrations of Mn3+ species (0-2 at%) in ZnO, evidenced the increased generation of cytotoxic SO species. Similar results were attained when Li, V and Ti were used as dopants.

Magnetic Nanosystems for Thermal Potentiation and Delivery of Chemotherapeutic Agents

(Eric Fuller, Shijian Wu, Carlos Rinaldi)

We are exploring the use of Flash NanoPrecipitation to generate Magnetic Composite NanoCarrriers (MCNCs) for encapsulation and magnetically triggered release of hydrophobic drug

cargos.

Cooling System: Compact Model

Using 3Dmodeling software, a preliminary compact prototype was designed. The purpose of this proto-type is to use it with confocal microscopy. The presented model, in Figure 5, will be made out of plasticto avoid distorting the magnetic field. A small section was added for the terminals of the coil and thethermocouple inside of it. Cold water will be introduced to the system to remove heat dissipated by thecoil. Since the magnetic field generated is very small, the top of the box has to be very thin and capableof holding the water running inside.

Figure 5: Compact Cooling System

Results

After constructing the series RLC circuit with the new capacitor setup, a few test runs were made. Forthis, a 1.0 kW amplifier was used. First, the resonant frequency was set up by monitoring the currentwhile increasing the frequency at 10.0 Vpp. Then, at the resonance frequency, the source voltage wasincreased slowly from 500.0 mVp till 5.10 Vp was reached. At this voltage, the coil was bubbling in thewater. The total forward power was approximately 500.0 W. After knowing the voltage, the system wasturned o↵ and on a couple of times to avoid the coil getting damaged due to the lack of a cooling system.The tests consisted of putting a screwdriver on top of the coil (not touching it) and letting it heat upby heating induction. The water at the tip of the screwdriver was evaporated and the heat was slowlyturning, the color of the tip, to blue. At Figure 6, the result can be appreciated.

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Figure 2: Temperature readings at 3.5 Vp�p for a water sample.

Figure 2 shows the temperature readings for the polycarbonate sheet (black), water sample (red), watercirculating through the cooling chamber (blue), and for the center of the coil (aqua-green). Input voltagewas at 3.5 Vp�p and the dial was set up at 5. The center of the coil maintained a safe temperature ( 70°C).The polycarbonate sheet and water sample temperatures rose up, meaning that they were being heatedup by dissipated heat from the coil. The water sample had a temperature of approximately 30°C atsteady state.

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Figure 3: Temperature readings at 3.5 Vp�p for a sample of 10mg/mL SPION concentration.

Figure 3 shows the temperature readings for the polycarbonate sheet (black), a sample of 10mg/mLSPION concentration (red), water circulating through the cooling chamber (blue), and for the center ofthe coil (aqua-green). With an AC voltage of 3.5 Vp�p and a dial of 6, the temperature at the center of thecoil raised to approximately 55°C. Water circulating through the coil maintained a temperature below

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Mechanisms of Thermal Resistance (Karem A. Court, Madeline Torres-Lugo, Carlos Rinaldi, Eduardo Juan)

Genomic analysis was employed to determine the underlying causes of thermal resistance and used to produce a therapeutic synergistic effect [1]

Development of Novel Tools for the Investigation of Nanomaterial/Tissue Interactions

(Jorge Castro, Reinaldo Agostini, Karla Ramos, Fernando Boria, Maribella Domenech, Madeline Torres-Lugo Carlos Rinaldi, Eduardo Juan)

Multi microwell culture arrays were developed to understand multicellular interactions [2,3]

Miniaturized coil prototype for live cell imaging was developed

Pure and Mn-doped ZnO Nanoparticles for 2-Photon Photodynamic Therapy (Yesusa Collantes and Oscar Perales-Perez)

Induced Structural Defects in Ti-doped ZnO and Its 2 Photon-Excitation (Milton A. Martínez Julca, Heidy Sierra and Oscar Perales-Pérez)

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Left: The shift of the main vibrations Raman modes is attributed to the distortion in the lattice caused by the incorporation of Ti species. Right: Normalized TPFM (690nm) emission spectra. The capability of ZnO and Ti-ZnO NPs capacity to be excited by 690 nm light opens new possibilities for light-induced bio-medical applications.

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A zebrafish testbed is used to determine nanomaterial toxicity in vivo in a high throughput manner. This model organism will also be used to evaluate quantum dots for PDT in cancer models.

Zebrafish Testbed in Photodynamic Therapy (Julio O. Acevedo, Oscar Perales-Perez, Martine Behra and Magda Latorre)

Zebrafish larvae exposed to nanomaterias

Toxic effects of ZnO NPs at high concentrations:

(a) edema, (b) necrosis

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References: [1] Court K.A. Rinaldi, C., Juan, E, Torres-Lugo, M., et al, Mol. Can. Ther. Submitted 2016 [2] Provisional patent 62/293,836, 2016, M. Domenech [3] Alvarez-Garcia, Y.R., Ramos, K., Boria, F., Domenech, M., et al. Lab of a Chip, Submitted 2016