Polymeric Nanoparticles Designed for Targeted Delivery of Anticancer Drugs

摘要

Active targeting of drugs to specific regions of the body, or even to specific regions of the cell, has become one of the most important objectives for the next generation of drug delivery systems. The introduction of various targeting ligands to drug delivery systems provides the broadest opportunities for drug targeting. Such smart drug delivery systems are capable of targeting specific cell types exclusively through ligand-receptor interactions. Monoclonal antibodies (mAbs) have been most frequently used as ligands for drug targeting to cancer cells due to the presence or over-expression of particular antigenic receptors on the surface of cancer cells. By covalent coupling of intact antibody molecules or the antigen-binding fragments on drug carriers, the drug is preferentially released at the cancer tissue or internalized within cancer cells following immunotargeting, which potentially enhances therapeutic efficacy and reduces systemic toxicity. Here we report the design of a novel polymeric nanoparticle system using new biodegradable graft copolymers of poly(2-methyl-2- carboxytrimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol)-furan, poly(TMCC-co-LA)-g-PEG-furan, that self-assemble into micellar nanoparticles in aqueous solution and provide reactive functional groups for Diels-Alder (DA) coupling chemistry of antibodies. We demonstrate the value of both this amphiphilic copolymer and the DA coupling chemistry in the development of immuno-nanoparticles by their specific and efficient binding with antigen over-expressing cell lines in vitro.