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Nanoscale Coordination Polymers for Synergistic NO and Chemodynamic Therapy of Liver Cancer

Yihui Hu1, Tian Lv1, Yu Ma1

  • 1State Key Laboratory of Natural Medicines, Department of Pharmaceutical Analysis and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases , China Pharmaceutical University , Nanjing 210009 , China.

Nano Letters
|March 29, 2019
PubMed

Insights

This study developed a novel nanoscale coordination polymer (NCP) for cancer therapy. The NCP releases nitric oxide (NO) and generates hydroxyl radicals (·OH) for synergistic NO-chemodynamic therapy (CDT), effectively inhibiting tumor growth.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Nitric oxide (NO) exhibits significant antitumor properties, including apoptosis induction and therapy sensitization.
  • Developing targeted NO delivery systems is crucial for enhancing cancer treatment efficacy and minimizing side effects.
  • Existing strategies often lack specificity, leading to off-target effects.

Purpose of the Study:

  • To design and synthesize a glutathione (GSH)-sensitive nanoscale coordination polymer (NCP) for targeted nitric oxide (NO) delivery.
  • To investigate the synergistic anticancer effects of NO combined with chemodynamic therapy (CDT) mediated by the NCP.
  • To evaluate the therapeutic efficacy of the novel nanomedicine in a preclinical tumor model.

Main Methods:

  • Synthesis of a nanoscale coordination polymer (NCP) using a GSH-sensitive NO donor (BPDB) and iron ions.
  • Characterization of the Fe(II)-BNCP for solubility, biocompatibility, and stability.
  • In vitro evaluation of NO release triggered by GSH and ·OH generation via Fenton activity in the presence of H2O2.
  • In vivo assessment of tumor growth inhibition in Heps xenograft ICR mouse models using the synergistic NO-CDT approach.

Main Results:

  • The synthesized Fe(II)-BNCP demonstrated good solubility, biocompatibility, and circulation stability.
  • High GSH concentrations in tumor cells triggered specific NO release from the NCP.
  • Fe(II)-BNCP effectively generated hydroxyl radicals (·OH) via Fenton reactions, contributing to CDT.
  • The combination of NO release and ·OH generation resulted in a synergistic cytotoxic effect, significantly retarding tumor growth in vivo.

Conclusions:

  • The developed Fe(II)-BNCP nanomedicine offers a promising strategy for synergistic nitric oxide-chemodynamic therapy (NO-CDT).
  • The GSH-sensitive design ensures targeted NO release within tumor microenvironments, enhancing specificity.
  • This work presents an efficient method for constructing coordination polymer nanomedicines using rationally designed prodrugs.
Keywords:
NO therapyNanoscale coordination polymerchemodynamic therapyliver cancersynergistic therapy

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