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journal article·2025-04Open access

Engineered a Gemcitabine Nano‐Prodrug Targeting Desmoplastic Pancreatic Tumor with Dual Enhancement of Penetration Dynamics

Qida Hu, Fu Zhang, Bowen Li, Piaopiao Jin, Junming Huang, Zhuo Yao, Xinyu Zhao, Shiyi Shao, Meng Wang, Yuan Ping, Tingbo Liang

Small· Volume 21· Issue 14
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Source abstract

Abstract

Abstract The desmoplastic nature characterized by dense tissue and poor vascular conditions in pancreatic cancer (PDAC) poses a significant barrier to effective chemotherapy. Targeting the extracellular matrix and reducing desmoplasia in the tumor microenvironment is a rational approach to improve the penetration and efficacy of gemcitabine (GEM) in PDAC. Herein, a small molecular self‐assembly nano‐prodrug is developed for the “three‐in‐one” co‐delivery of GEM chemotherapeutics, all‐trans retinoic acid (ATRA), and nitric oxide (NO) donors, decorated with PDAC‐homing targeting peptide. Stimulated by the PDAC microenvironment, the nano‐prodrug releases ATRA that quiesces activated pancreatic stellate cells to alleviate stromal desmoplasia. Simultaneously, it generates abundant NO to induce a vasodilatory effect as well as a “nanomotor” effect. This combinational nano‐prodrug delivery strategy, with a dual enhancement of drug penetration dynamics, effectively improves the distribution and bioavailability of the co‐delivered GEM into the deep and dense pancreatic tumor tissue, which leads to significant amplification of tumor growth inhibition in different PDAC mouse models.
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Research context

Nanomaterials

OpenAlex topics: Pancreatic and Hepatic Oncology Research · Nanoparticle-Based Drug Delivery · Cancer Cells and Metastasis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China

Department of Chemical and Biomolecular Engineering National University of Singapore 4 Engineering Drive Singapore 117585 Singapore

Healthcare Management Center First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

Zhejiang Provincial Key Laboratory of Pancreatic Disease Hangzhou 310003 China

Innovation Center for the Study of Pancreatic Diseases Hangzhou 310003 China

Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary & Pancreatic Diseases Hangzhou 310003 China

Cancer Center Zhejiang University Hangzhou 310058 China

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China · Natural Science Foundation of Zhejiang Province

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