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Pharmacokinetics modulation in solid tumors through thrombin-embedded nanomedicine.

Sheng Lin1, Liuwei Zhang2, Hongyan Cui2

  • 1The State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200433, China.

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|April 4, 2025
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Summary

This study introduces a novel dual prodrug nanomedicine that targets cancer cells and releases chemotherapy drugs within tumors. The nanomedicine enhances drug distribution and retention, improving anti-tumor efficacy.

Keywords:
NanomedicineProdrug nanomedicineSolid tumorSynergistic anticancer therapyTargeted drug deliveryTumor microenvironment-responsive

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Developing effective anti-tumor nanomedicines faces challenges in sustained drug retention and distribution within tumors.
  • Achieving precise spatiotemporal control over drug release is crucial for maximizing therapeutic outcomes.

Purpose of the Study:

  • To develop a multifaceted prodrug nanomedicine with precise spatiotemporal responsiveness for enhanced anti-tumor therapy.
  • To investigate the role of dual prodrugs (redox-responsive SN38 and pH-responsive thrombin) in drug release and tumor targeting.

Main Methods:

  • Integration of dual prodrugs: redox-responsive SN38 and pH-responsive thrombin into a nanomedicine.
  • Spatial selectivity directed by integrin overexpression on cancerous cells.
  • Induction of vascular occlusion by thrombin to normalize tumor interstitial fluid pressure.

Main Results:

  • The nanomedicine demonstrated precise drug release in response to tumor acidity and reductive stress.
  • Thrombin-induced vascular occlusion promoted massive intratumoral distribution and sustained retention of SN38.
  • Advanced mass spectrum mapping validated SN38 prodrug activation and widespread tumor distribution, unlike conventional nanomedicines.

Conclusions:

  • The developed dual prodrug nanomedicine effectively targets cancer cells and induces vascular occlusion.
  • This approach facilitates massive intratumoral drug distribution and sustained drug retention, enhancing cytotoxic potency.
  • The nanomedicine orchestrates controlled chemotherapy release, offering a promising strategy for improved anti-tumor therapy.