Synthesis of Multi Responsive Hybrid Polymer Microgels for biomedical sensing and catalytic applications

Initially, the issue of massive drug delivery deep into tumor tissue has been addressed. For this purpose dual stimuli-responsive polyplex micelles systems have been designed from self-assembly of anionic block copolymers and platinum(IV)-conjugated cationic poly(amidoamine) (PAMAM-Pt(IV)) dendrimer prodrugs as a drug delivery. In anionic block copolymer, charge conversion occurs in response to mild acidic environment at tumor site (pH ~ 6.8). As a result of the charge conversion, there occur an electrostatic repulsion which permitting rapid disassembly of the polyplex micelle. Due to disassembly of the polymer micelles, PAMAM-Pt(IV) prodrug is released in the form of individual molecules, exert deep penetration and well-dispersion activity in the tumor tissue by virtue of its small size and high mobility. Furthermore, the well-dispersed positively charged PAMAM dendrimers having high affinity toward the negatively charged cellular membrane which help them to efficiently internalize into the tumor cells, followed by release of active cisplatin drug in the reductive cytosol. This anticancer drug delivery platform provides a unique two-step delivery of anticancer drug for pursuit of deep tumor tissue penetration and overcoming drug resistance. Later on multi-responsive poly(NIPAM-co-DMAEMA) microgels are synthesized by free radical emulsion polymerization. Swelling and deswelling properties of the prepared microgels are investigated in response to change in pH and temperature of the system. The prepared microgels show a lower critical solution temperature (LCST) at about 34 °C and pKa value of 7.3 for DMAEMA monomer. The microgels are used as microreactor as well as scaffold for gold nanoparticles (Au-NPs). Different parameters like temperature, concentration of Au-NPs and content ratio of DMAEMA monomers are studied to show their effect on size and volume phase transition temperature (VPTT) of poly(NIPAM-co-DMAEMA) microgels. It is observed that the microgel particle size decreases with increase in all of the above mentioned parameter. Optical properties of Au-NPs are studied by UV-Visible spectroscopy and red shift is observed both with increase in concentration of chlorauric acid and sodium borohydride, respectively. Similarly red shift is observed by increasing temperature of Au-NPs loaded microgel composite in the range of 25 to 50 °C. Moreover, poly(NIPAM-coDMAEMA)/Au-NPs composites can act as excellent catalyst for reduction of 4-nitrophenol and the catalytic activity of the composite microgel can be controlled by changing temperature of the system. Onward the synthesized cross-linked polymer microgels are doped with a fluorescent dye by free radical emulsion polymerization. Thermo-responsive behavior and microenviroment of the dye doped microgel particles are studied by fluorescence and optical transmittance. It is observed that turbidity of the microgel system start to increase after VPTT due to shrinkage of the microgel network. A dramatic increase in relative fluorescence intensity and wavelength at maximum fluorescence intensity (?max) also occur due to increase in hydrophobic environment around the dye molecules with shrinkage of the microgel system. The poly(NIPAM-co-DMAEMA-co-NBDAA) microgel particles are used for in-situ synthesis of Au-NPs which results in fluorescent quenching of the microgels through Förster Resonance Energy Transfer (FRET) process. The morphology of microgels is observed by Transmission Electron Microscopy (TEM). At the end a novel ferric-phosphate induced shape memory (SM) hydrogels are synthesized by one-step copolymerization of isopropenyl phosphonic acid (IPPA) and acrylamide (AM) in the presence of a cross-linker. The synthesized Shape Memory (SM) Hydrogel is different from traditional ones as our system can be modified into various shapes and can be recovered to its original shape by using different external conditions such as reducing agent or a competitive complexing agent. This unique feature is due to the reason that ferric ions show a high affinity for complexation with phosphate groups of IPPA, which acts as a physical cross-linker to form the secondary networks within the hydrogels to induce the shape memory effect which is totally reversible