Amphiphilic Glycopolymer Nanoparticles for pH-Responsive Paclitaxel Delivery and Enhanced Efficacy in Pancreatic Ductal Adenocarcinoma Therapy

Pancreatic ductal adenocarcinoma (PDAC) presents significant therapeutic challenges due to drug resistance, systemic toxicity, and poor drug solubility. We developed amphiphilic ABC-type glycopolymer nanoparticles (mPEG-b-PCL-b-PGP) [PCG] for the targeted delivery of paclitaxel (PTX). PCG was synthesized via ring-opening polymerization and atom transfer radical polymerization, followed by deacetylation. Structural and thermal characterizations were performed using ¹H-NMR, FT-IR, GPC, TGA, and DSC to confirm block composition, molecular weight, and stability of the glycopolymer. PTX-loaded PCG nanoparticles [PCG(PTX)] exhibited high drug loading capacity, colloidal stability, and pH-responsive drug release. In vitro, PCG(PTX) demonstrated selective uptake by PDAC cells and enhanced cytotoxicity. Combination with gemcitabine (Gem) further reduced viability and migration while promoting apoptosis. In orthotopic PDAC mouse models, PCG(PTX) + Gem significantly suppressed tumor growth, prolonged survival, and tolerability compared with free PTX. These results demonstrate the promise of PCG glycopolymer nanoparticles as an effective platform for targeted, combination chemotherapy in PDAC.