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Programmed-response cross-linked nanocarrier for multidrug-resistant ovarian cancer treatment

Haijing Qu1, Jinfan Yang2, Shuaijun Li3

  • 1Department of Oncology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA; School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|March 23, 2023
PubMed

Insights

This study developed novel disulfide cross-linked micelles (PDCM) for enhanced delivery of chemotherapy drugs like paclitaxel. These micelles effectively target multidrug-resistant ovarian cancer, improving drug release and therapeutic efficacy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Chemotherapeutic drug limitations include poor solubility, side effects, and multidrug resistance (MDR).
  • Polymeric micelles offer a potential solution for improved drug delivery.
  • Previous work established well-defined dendrimers for micelle development.

Purpose of the Study:

  • To optimize and synthesize programable-released disulfide cross-linked micelles (PDCM).
  • To evaluate PDCM carrying betulinic acid (BA) and paclitaxel (PTX) for treating MDR ovarian cancer.
  • To assess the enhanced pharmacokinetic profile and tumor penetration of PTX delivered via PDCM.

Main Methods:

  • Synthesis of programable-released disulfide cross-linked micelle (PDCM) nanoparticles.
  • Encapsulation of betulinic acid (BA) and paclitaxel (PTX) into PDCM (PDCM@PTX).
  • Evaluation of therapeutic efficacy in multidrug-resistant (MDR) ovarian cancer mouse models.

Main Results:

  • PDCM@PTX formed stable nanoparticles, improving paclitaxel's pharmacokinetic profile and circulation time.
  • Enhanced tumor penetration of PDCM@PTX was observed.
  • Programable-switches (ester bonds, disulfide cross-linking) cleaved in the tumor microenvironment (glutathione, esterase) enabling in situ drug release.

Conclusions:

  • PDCM nanoparticles effectively deliver BA and PTX to MDR ovarian tumors.
  • The smart micelle design facilitates targeted drug release within the tumor microenvironment.
  • PDCM@PTX demonstrated intensive therapeutic efficacy against MDR ovarian cancer.
Keywords:
Cross-linkingEsterase responseGSH responseMultidrug resistantOvarian cancer

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