2. Academic Validation
  3. Amphiphilic Glycopolymer Nanoparticles for pH-Responsive Paclitaxel Delivery and Enhanced Efficacy in Pancreatic Ductal Adenocarcinoma Therapy

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

  • ACS Appl Bio Mater. 2026 Jun 1;9(11):4723-4739. doi: 10.1021/acsabm.5c02077.
Naga Malleswara Rao Nakka 1,  Hari Krishnareddy Rachamala 1,  Nagamalleswara Rao Indla 2 3,  Zain Toiemie 1,  Ramcharan S Angom 1,  Shamit Kumar Dutta 1,  Enfeng Wang 1,  Santanu Bhattacharya 1 4,  Krishnendu Pal 1,  Annadanam V Sesha Sainath 2 3,  Debabrata Mukhopadhyay 1 4
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences, Jacksonville, Florida 32224, United States.
  • 2 Polymers and Functional Materials and Fluoro-Agrochemicals Department, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India.
  • 3 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • 4 Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Sciences, Jacksonville, Florida 32224, United States.
PMID: 42138136 DOI: 10.1021/acsabm.5c02077
Abstract

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.

Keywords

amphiphilic glycopolymer nanoparticles; atom transfer radical polymerization; combination therapy; pH-responsive release; paclitaxel delivery; pancreatic ductal adenocarcinoma.

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