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Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Related Experiment Video

Updated: Sep 9, 2025

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
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Nano-enabled repurposing of Benproperine phosphate enhances pancreatic Cancer chemotherapy through lethal autophagy

Zhe Zhang1, Qitai Chen2, Rujia Zheng1

  • 1Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; MOE Joint International Research Laboratory of Pancreatic Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|September 3, 2025
PubMed
Summary

This study developed a novel nanoplatform combining benproperine phosphate (BPP) and gemcitabine (Gem) to overcome pancreatic cancer treatment resistance. The nanoplatform enhances chemotherapy by blocking autophagy and activating immune responses.

Keywords:
AutophagyImmune activationNano-enabled drug repurposingPancreatic cancerZeolitic imidazolate framework-8 (ZIF-8)

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Evaluating Autophagy Levels in Two Different Pancreatic Cell Models Using LC3 Immunofluorescence
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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Gemcitabine chemotherapy is standard for pancreatic cancer but faces challenges with drug delivery and resistance, including autophagy.
  • Developing novel strategies to enhance gemcitabine efficacy and overcome resistance is crucial for improving patient outcomes.

Purpose of the Study:

  • To develop a hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) nanoplatform for co-delivering benproperine phosphate (BPP) and gemcitabine (Gem) to treat pancreatic cancer.
  • To investigate the synergistic effects of BPP and Gem delivered via the nanoplatform, focusing on overcoming autophagy-mediated resistance and stimulating anti-tumor immunity.

Main Methods:

  • Fabrication of a hyaluronic acid (HA)-modified ZIF-8 nanoplatform encapsulating BPP and Gem (HA/ZIF-8@BPP/Gem).
  • Evaluation of drug release, cytotoxicity, and synergistic effects in pancreatic cancer cell lines and in vivo models (patient-derived xenografts, orthotopic tumors).
  • Mechanistic studies using RNA sequencing and flow cytometry to analyze autophagy pathways and immune responses.

Main Results:

  • The HA/ZIF-8@BPP/Gem nanoplatform demonstrated rapid release of BPP and Gem in the acidic tumor microenvironment, leading to synergistic cytotoxicity.
  • BPP was found to initiate autophagy but inhibit autophagosome-lysosome fusion, converting Gem-induced protective autophagy into a lethal process.
  • The nanoplatform activated immune responses, particularly T cell-mediated immunity, by stimulating the secretion of immune-related cytokines.

Conclusions:

  • Nano-enabled drug repurposing with HA/ZIF-8@BPP/Gem offers a safe and effective strategy to enhance pancreatic cancer chemotherapy.
  • This approach improves outcomes by inducing amplified autophagy arrest and activating anti-tumor immune responses.