Glucose-modified PEG-PLA self-assembled nano-micelles optimize DOX enrichment, tissue penetration, and tumor suppression effects in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) poses significant therapeutic challenges due to its unique tumor microenvironment, which is characterized by collapsed blood vessels and elevated intratumoral pressure, severely hindering drug penetration and distribution. Consequently, we synthesized glucose-modified PEG-PLA (polyethylene-polylactice acid) nanoparticles as a drug delivery system for doxorubicin (DOX). We successfully enhanced the permeability and targeting capability of the nanoparticles in pancreatic cancer cells using glycosylation modification, significantly increasing drug accumulation within the tumor microenvironment. Our study demonstrated excellent cellular uptake of the nanoparticles in vitro and their improved penetration in 3D tumor spheroid models. Additionally, in vivo experiments revealed a notable increase in nanoparticle accumulation at the tumor site, along with favorable drug release characteristics. Hence, glucose-modified PEG-PLA nanoparticles hold substantial potential for clinical application in PDAC treatment, effectively enhancing the therapeutic efficacy of chemotherapeutic agents.