L-Amino acid Based Polyester Nanocarriers for Drug Delivery and Bio-imaging
The past generation therapeutic agents are increasingly failing in combating new-age threats. Therapeutics based on polymers are advantageous as they possess advanced targeting, can target hard to reach agents, and carry multiple cargos of conflicting nature. These can be extremely selective, owing to several phenomena such as Enhanced Permeation (EPR) effect and carrying multiple cargoes in a single particle, which can have synergistic effects, leaving them more potent than any of the medicine alone.
L-Amino acid-based synthetic polypeptides non-peptides are extensively explored for biomedical applications owing to their structural diversity and biocompatibility. My talk 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 bioimaging in cancer cells. These polymers were designed with the dual response to acidic conditions and enzyme-rich environment stimuli. Different therapeutically active drugs were loaded into the polymer scaffolds, and their cytotoxicity was studied in the cancer cell lines.
The uptakes of these drugs were monitored using confocal microscopy. L-amino acid-based amphiphilic luminescent polyester was developed using π- conjugated oligo-phenylenevinylene (OPV) custom made diols, while Aggregation induced emission (AIE) capable hydroxyl functionalized tetraphenylethyelene (TPE) diol was tailor-made through multi-step reaction and was subjected to melt transesterification with L-aspartic acid monomer to yield new blue-luminescent amphiphilic polyesters.
Hydroxyl and carboxylic functionalized polyesters were also synthesized. The hydrophilic hydroxyl and carboxylic groups along with the hydrophobic aliphatic backbone made these polymer amphiphilic in nature and enabled these to self-assemble into spherical nanoparticles in water, which exhibited superior encapsulation capabilities to load wide ranges of both water-soluble and water-insoluble anticancer drugs and fluorophores. The amphiphilic polyesters designed and developed based on L-aspartic acid residues presented in the talk are new entries as enzymatic-biodegradable polymers in the literature, and the custom-designed OPV-tagged and TPE-tagged fluorescent polymers are excellent nano-scaffolds for constructing a wide range of FRET probes with drugs and fluorophores which could be employed for early diagnostics of cancer and other bio-imaging applications. Thus, the work opens up a new platform of opportunities in the biomaterials arena based on L-Amino acid polymers.