Development of Size-convertible Nanoparticles for Deep Tumor Penetration

Abstract

For several decades, various kinds of drug delivery system (DDS) have been researched for efficient tumor treatment method that can overcome limitation of drug itself, such as low stability, low water-solubility, and nonspecific treatment. Among many candidates of drug carriers, polymeric micelle is frequently studied because of its facile synthesis and tunable size. In our study, PEG-PDS block copolymer with hydrophilic and hydrophobic segments was synthesized to form proper size-convertible micelles. Amphiphilic copolymers are known to self-assemble in solution. Through disulfide intracrosslinking of PDS group, micelles can be locked to form nanogel. Polyethylene glycol monomer can reduce nonspecific interaction of nanoparticles with biomolecules in body fluids, which is stealth effect, and can make larger aggregates above LCST. Size-convertible property is important to avoid body clearance and passively target loose tumor blood vessels by large size, but to penetrate deep into tissue after reaching the target site. We tried to design nanocarriers which are large during blood circulation and small in response to tumoral condition. For that, large aggregates fixed with MMP-degradable peptide ligands will be able to release drug inside through degradation under rich MMP condition, which is overexpressed in tumor tissue. Further studies will be performed to see the behavior of nanoparticles.