Santaneel Ghosh

Refractive Index Change Due to Volume-Phase Transition in Polyacrylamide Gel Nanospheres for Optoelectronics and Bio-photonics

Poly(N-isopropylacrylamide) (PNIPAM) hydrogel nanospheres response to global temperature stimuli across the low critical solution temperature is studied as the water content in the polymer network is modified. The refractive index of gel nanoparticles was measured as a function of temperature using spectroscopic ellipsometry. The volume of the nanospheres reduces by 40% resulting in a modification of light scattering properties of the medium. A change in temperature from 33 to 34 °C results in a volume contraction of nanospheres which is accompanied by 8–10% enhancement in the refractive index of the gel network.

Oscillating magnetic field-actuated microvalves for micro- and nanofluidics

The feasibility of using tunable magnetic nanoparticles embedded in cylindrical hydrogel materials as a flow regulator via thermo-mechanical gating is studied within microfluidic channels. Ferromagnetic nanoparticles (Fe3O4) encapsulated within a thermo-sensitive polymer network (-poly(N-isopropylacrylamide) (PNIPAM)) was polymerized inside 300 µm diameter micro-capillary tubes. An oscillating magnetic field range 20–125 Oe, (100–1000 kHz) was used to induce heat and control the valving action. Valving action was effectively regulated by modulating the magnetically responsive PNIPAM networks (MPNIPAM) and thereby physically regulating the harmonics (swelling and shrinking) of the polymer monolith inside the microchannel. Magnetic properties in terms of saturation magnetization, remanence and coercivity of the designed system have been extracted for data accuracy. The optimum concentration of NIPAM monomer in the polymer matrix and the embedded nanoparticles yield ~80% volume shrinkage inside the microchannel, which is close to the undoped PNIPAM system, without compromising the oscillating field induced heating. Very importantly, the oscillating field-actuated de-swelling response time is ~3 s, which is significantly faster than the thermal actuation, and in addition the microvalve exhibits a faster response time compared with the macrovalve (MPNIPAM monolith inside 1500 µm diameter channel). The enhanced shrinkage rate and the actuation efficiency might be ideal for many biomedical applications, including synergistic application of heat and sustained releasing capability of chemotherapeutic agents.

Alternating Magnetic Field Controlled, Multifunctional Nano-Reservoirs: Intracellular Uptake and Improved Biocompatibility

Biocompatible magnetic nanoparticles hold great therapeutic potential, but conventional particles can be toxic. Here, we report the synthesis and alternating magnetic field dependent actuation of a remotely controllable, multifunctional nano-scale system and its marked biocompatibility with mammalian cells. Monodisperse, magnetic nanospheres based on thermo-sensitive polymer network poly(ethylene glycol) ethyl ether methacrylate-co-poly(ethylene glycol) methyl ether methacrylate were synthesized using free radical polymerization. Synthesized nanospheres have oscillating magnetic field induced thermo-reversible behavior; exhibiting desirable characteristics comparable to the widely used poly-N-isopropylacrylamide-based systems in shrinkage plus a broader volumetric transition range. Remote heating and model drug release were characterized for different field strengths. Nanospheres containing nanoparticles up to an iron concentration of 6 mM were readily taken up by neuron-like PC12 pheochromocytoma cells and had reduced toxicity compared to other surface modified magnetic nanocarriers. Furthermore, nanosphere exposure did not inhibit the extension of cellular processes (neurite outgrowth) even at high iron concentrations (6 mM), indicating minimal negative effects in cellular systems. Excellent intracellular uptake and enhanced biocompatibility coupled with the lack of deleterious effects on neurite outgrowth and prior Food and Drug Administration (FDA) approval of PEG-based carriers suggest increased therapeutic potential of this system for manipulating axon regeneration following nervous system injury.

Role of engineered nanocarriers for axon regeneration and guidance: current status and future trends.

There are approximately 1.5 million people who experience traumatic injuries to the brain and 265,000 who experience traumatic injuries to the spinal cord each year in the United States. Currently, there are few effective treatments for central nervous system (CNS) injuries because the CNS is refractory to axonal regeneration and relatively inaccessible to many pharmacological treatments. Smart, remotely tunable, multifunctional micro- and nanocarriers hold promise for delivering treatments to the CNS and targeting specific neurons to enhance axon regeneration and synaptogenesis. Furthermore, assessing the efficacy of treatments could be enhanced by biocompatible nanovectors designed for imaging in vivo. Recent developments in nanoengineering offer promising alternatives for designing biocompatible micro- and nanovectors, including magnetic nanostructures, carbon nanotubes, and quantum dot-based systems for controlled release of therapeutic and diagnostic agents to targeted CNS cells. This review highlights recent achievements in the development of smart nanostructures to overcome the existing challenges for treating CNS injuries.

Controlled actuation of alternating magnetic field-sensitive tunable hydrogels

The feasibility of using tunable magnetic nano-particles embedded in cylindrical hydrogel materials for guided actuation via controlled modulation of oscillating magnetic field and frequency is investigated. Ferromagnetic nano-particles (Fe3O4) encapsulated within a thermo-sensitive polymer network [-poly(N-isopropylacrylamide) (PNIPAM)] were polymerized inside 1.5?mm diameter capillary tubes. Inside alternating magnetic field (25?70?Oe, 150?280?kHz), the polymer monolith quickly bends along the longitudinal axis. The bending behaviour of the polymer monolith was influenced by the following factors: (a) mechanical strength of the monolith, (b) ac field-induced temperature regulation and (c) the surface evaporation. The equilibrium bending angle reached a maximum value of 74? at 30?Oe, 200?kHz, between 15% and 35% relative humidity conditions. In addition, we found that micro-scale monolith (300??m diameter) exhibited significantly faster actuation response compared with the 1500??m diameter hydrogel cylinder. Both de-swelling efficiency and volumetric transition temperature were not affected due to the nano-magnet incorporation. As ac magnetic field-induced controlled modulation can directly transform the absorbed energy into bending and shrinkage simultaneously for temperature sensitive polymers, i.e. the absorbed energy is converted into mechanical work, this novel approach may lead to a new category of magnetically responsive polymeric structures for potential applications in the field of smart gel-based devices, such as micro-sensors and actuators, and particularly in biomedical fields.

Excellent biocompatibility of semiconductor quantum dots encased in multifunctional poly(N-isopropylacrylamide) nanoreservoirs and nuclear specific labeling of growing neurons

Quantum dots (QDs) have received attention for labeling biomolecules; however, toxicity of these nanostructures in the intracellular environment has prevented a biomedical breakthrough. Here we report biocompatibility of a QD based multifunctional system on neuronal cells. Moreover, the designed nanostructures bind with high affinity in the cell nucleus. Nucleus specific binding and enhanced biocompatibility, coupled with no deleterious effects on neurite outgrowth, even at high dosages (500 μg/ml sphere conc.) suggest increased therapeutic potential of this system for specific targeting followed by controlled release of drugs in treating neurodegenerative disorders.

Enhanced Luminescence Efficiency from Hydrogel Microbead Encapsulated Quantum Dots

In this paper, a novel quantum dot (QD) based nanomaterial system is presented for efficient FRET analysis. The quantum dots have been embedded in hydrogel microspheres based on poly(N-isopropylacrylamide) (PNIPAM) a thermoresponsive polymer that undergoes a volume phase transition across the low critical solution (LCST). The optical properties of the quantum dots entrapped within the gel microspheres has been modified due to change in refractive index, volume density of the surrounding hydrogel medium. The QDs encapsulated in the PNIPAM microspheres showed 100–200 % enhancement in the PL efficiency as the microgels shrank at the temperature above the LCST temperature of the gel.

Engineered, thermoresponsive, magnetic nanocarriers of oligo(ethylene glycol)-methacrylate-based biopolymers

Engineered magnetic nanocarriers offer attractive options for implementing novel therapeutic solutions in biomedical research; however lack of biocompatibility and external tunability have prevented a biomedical breakthrough. Here we report multifunctional, magnetic nanospheres with tailored size, volumetric transition range, and magnetic properties based on biocompatible, thermo-responsive oligo(ethylene glycol) methacrylate biopolymers. Precise control of the nanosphere size in the range 100–300 nm, coupled with a higher and broader volumetric transition range (32–42 °C), is ideal for various biomedical applications. More importantly, super-paramagnetic behavior of the nanocarriers, even after polymer shell shrinkage, indicates stable and easily controllable loss mechanisms under exposure to an ac magnetic field.

CdTe quantum dot in tunable hydrogel nanocrystals

Optical emission from CdTe quantum dots (QDs) embedded in poly-N-isopropylacrylamide hydrogel nanocrystallites can be enhanced over 100% using thermal and electrical stimulus. Relative distance amongst QDs was modified tuning the hydrogel facilitating resonant energy transfer.

Photo-Magnetic Irradiation-Mediated Multimodal Therapy of Neuroblastoma Cells Using a Cluster of Multifunctional Nanostructures

The use of high intensity chemo-radiotherapies has demonstrated only modest improvement in the treatment of high-risk neuroblastomas. Moreover, undesirable drug specific and radiation therapy-incurred side effects enhance the risk of developing into a second cancer at a later stage. In this study, a safer and alternative multimodal therapeutic strategy involving simultaneous optical and oscillating (AC, Alternating Current) magnetic field stimulation of a multifunctional nanocarrier system has successfully been implemented to guide neuroblastoma cell destruction. This novel technique permitted the use of low-intensity photo-magnetic irradiation and reduced the required nanoparticle dose level. The combination of released cisplatin from the nanodrug reservoirs and photo-magnetic coupled hyperthermia mediated cytotoxicity led to the complete ablation of the B35 neuroblastoma cells in culture. Our study suggests that smart nanostructure-based photo-magnetic hybrid irradiation is a viable approach to remotely guide neuroblastoma cell destruction, which may be adopted in clinical management post modification to treat aggressive cancers.