Structural Engineering of Amphiphilic Block Copolymer Nano-assemblies for Cancer Therapy

Abstract

This thesis is aimed to design and develop amphiphilic polycaprolactone (PCL) block copolymer nanoscaffolds for intracellular drug delivery in cancer therapy. The amphiphilicity in the PCL block copolymer was accomplished through bishydroxyl substitution in the periphery of PCL backbone. For this purpose, a new γ-substituted caprolactone monomer containing silyl protected hydroxyl groups was tailor-made by multistep synthesis. The monomer underwent ring opening polymerization (ROP) by a newly designed naphthol based initiator to yield homopolymers and block copolymers. Silyl groups were deprotected to yield hydroxyl functionalized homo and block copolymers. Monomer and polymers were characterized using 1H NMR, 13C NMR, FTIR and HRMS and the molecular weights of the polymers were determined by gel permeation chromatography (GPC). Thermogravimetric analysis showed that the polymers were thermally stable up to 240 oC. Differential scanning calorimetry and polarized light microscope (PLM) techniques were used to study the semi-crystalline and amorphous natures of the polymers. Water contact angle (WCA) of the silyl-polymers were found be in the range of 90-100 with respect to hydrophobic nature. Whereas, the hydroxyl polymers were found to have WCA< 50 with respect to hydrophilic nature. These block copolymers selfassembled in water to produce micellar nanoparticles of <200 nm size. These nanoparticles were capable of encapsulating anticancer drugs like doxorubicin with excellent drug loading capabilities. These drugs loaded nanoparticles were characterized by dynamic light scattering (DLS) and electron microscopy. Enzymatic degradation of the polymers was studied using Dynamic light scattering (DLS). Confocal and flow cytometry analysis confirmed the cellular uptake of the doxorubicin loaded polymer nanoparticles in cancer cells.