Multifunctional polymer nanoparticles for liposarcoma treatment

Abstract

Liposarcoma is a rare cancerous tumor that primarily originates in the fatty tissues of the body, commonly in the lower limbs and retroperitoneal regions. It can be classified into four subtypes and among them, well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) most frequently occur. Treatment options for liposarcoma include surgery, radiation therapy, and chemotherapy. However, these treatments are generally limited. In this thesis, the potential of multifunctional polymer nanoparticles that can target and disrupt liposarcoma cells was assessed. Polymeric nanoparticles were prepared from poly(D,L-lactide-co-glycolide) (PLG) and calcium carbonate, following chemical modification with an adipocyte-targeting peptide. These nanoparticles were designed to release carbon dioxide gas within the acidic endosomal pH environment after cellular uptake, aiming to disrupt the membrane of WDLPS cells. The uptake efficiency of nanoparticles was significantly enhanced by WDL cells after modification of the nanoparticles with ATS peptide. Furthermore, generation of carbon dioxide gas from the nanoparticles induced cell death through necrosis. This innovative strategy may address the imperative to develop functional polymer nanoparticles as safe and effective anticancer agents.