Synthesis and biological profile of novel three-arms star-shaped PLA-PEG amphiphilic copolymers

Star polymers based on amphiphilic polylactide-poly(ethylene glycol) (PLA-PEG) are biomaterials of growing interest in the biomedical field as injectable drug delivery systems. Their exclusive structure, consisting of multiple variable-length linear chains (arms) radiating from a central core, is responsible for remarkable properties unattainable by linear polymers. [1,2] In the framework of our studies dealing with the synthesis and functionalization of biopolymers for drug delivery purposes, [3-6] we have recently designed and synthesized a three-arms star-shaped PLA-PEG copolymer decorated with the integrin-targeting RGD peptide (starPLA-PEG-RGD), a cell recognition motif highly expressed in tumor cells and strongly involved in the regulation of tumor angiogenesis. Taking advantages from the recent advances in polymerization strategies and coupling chemistry, the synthesis of this complex macromolecular architecture was developed in a core-first approach, combining the Ring Opening Polymerization (ROP) with the click chemistry. The multi-step synthetic route allowed precisely controlled molecular weights and proper functionalities. The star polymers were fully characterized by 1HNMR spectroscopy, gel permeation chromatography (GPC) and MALDI-ToF analysis. Two model anticancer drugs, Doxorubicin (DOX) and Docetaxel (DTX), were efficiently encapsulated into the starPLA-PEG nanoparticles (NPs) by nanoformulation approaches (e.g. dialysis and nanoprecipitation); the particle size and size distribution, zeta potential, drug loading and encapsulation efficiency were investigated. Moreover, the biological profile of drug-loaded starPLA-PEG NPs was explored with the aim to evaluate the cytotoxicity and antiproliferative activity against different tumoral cell lines (e.g. osteosarcoma, glioblastoma and breast cancer cells).