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Macromolecular NO-Donor Micelles for Targeted and Augmented Chemotherapy against Prostate Cancer

Jiaxin Chen1, Bingbing Zhao1, Junhui Zou1

  • 1Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, 210009, China.

Advanced Healthcare Materials
|November 23, 2022
PubMed

Insights

This study developed a novel nanoplatform for prostate cancer (PCa) chemotherapy. The bombesin-installed micelles deliver mitoxantrone (MTO) and nitric oxide (NO) to tumor cells, enhancing MTO

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Mitoxantrone (MTO) is used for prostate cancer (PCa) but has suboptimal outcomes.
  • Poor drug delivery and tumor resistance mechanisms (DNA repair, anti-oxidation) limit MTO efficacy.

Purpose of the Study:

  • To develop a targeted nanoplatform for enhanced MTO chemotherapy in PCa.
  • To combine MTO with nitric oxide (NO) as a sensitizer for improved therapeutic outcomes.

Main Methods:

  • Fabrication of bombesin-installed, MTO-loaded polymeric micelles containing a macromolecular NO-donor (BN-NMMTO).
  • Utilizing bombesin for active targeting and accumulation in PCa.
  • Intracellular NO release via glutathione (GSH) and subsequent MTO release.

Main Results:

  • BN-NMMTO effectively targeted and accumulated in PCa sites, with internalization into tumor cells.
  • Intracellular NO release inhibited DNA repair and anti-oxidation pathways, sensitizing MTO.
  • Targeted MTO release induced DNA lesions and reactive oxygen species (ROS) in tumor cells without harming normal cells.

Conclusions:

  • The developed BN-NMMTO nanoplatform offers targeted NO-sensitized chemotherapy for PCa.
  • This approach overcomes MTO resistance mechanisms, enhancing its cytotoxicity and therapeutic potential.
Keywords:
DNA lesionsmitoxantronenitric oxideoxidative stresstargeted prostate cancer therapy

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