L amino acid based polyester nanocarriers for drug delivery and bioimaging

Abstract

This thesis work is aimed to explore new classes of amphiphilic and biodegradable polyester and their fluorescent nano assemblies based on natural L aspartic acid resources for accomplishing anticancer drug delivery and intracellular bio imaging in cancer cells L aspartic acid resource was converted into multi functional monomer and it was polymerized under melt conditions in the presence of hydrophilic and hydrophobic diols to yield amphiphilic copolymers These polymers were designed in order to possess inbuilt pH responsive BOC urethane hanging groups and esterase responsive ester backbone making them dual stimuli containing amphiphilic polyesters The BOC urethanes underwent cleavage and transformation into cationic moieties NH3 in the highly acidic endosomal compartments of the intracellular regions trigger 1 The ester containing backbone was susceptible to cleave under the presence of esterase enzyme present in the hydrolytic enzyme rich lysosomes which acts as the trigger 2 Three different therapeutically active drugs curcumin CUR doxorubicin DOX and topotecan TPT were loaded into the polymer scaffolds and their cytotoxicity were studied in breast cancer MCF 7 and cervical HeLa cancer cell lines The uptake of these drugs was monitored using confocal microscopy Further L amino acid based amphiphilic luminescent polyester was developed using 960 conjugate luminescent materials and their FRET fluorescence resonance energy transfer probes for colour tunable intracellular imaging were demonstrated Highly luminescent oligo phenylenevinylene OPV with 960 conjugated cores were tailor made into melt polymerisable diols and were subjected to thermo selective melt trans esterification polymerization with modified multi functional L aspartic acid monomers along with hydrophilic tri ethylene glycols and hydrophobic dodecanediol to yield OPV labelled luminescent amphiphilic polyesters Comprehensive photo physical analyses exhibited that the OPV and NR a hydrophobic encapsulated dye were constricted within clos