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Related Experiment Video

Updated: May 16, 2025

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Evodiamine-Based Nitroreductase Responsive Theranostic Agents for Treatment of Colon Cancer.

Keliang Li1, Yuhang Sun1, Zonglin Ma2

  • 1The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), Shanghai 200433, China.

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|April 2, 2025
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Summary
This summary is machine-generated.

New theranostic agents target solid tumors by activating prodrugs in hypoxic environments. Probe-2 demonstrated significant tumor growth inhibition with low toxicity in preclinical models.

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Area of Science:

  • Oncology
  • Biomedical Engineering
  • Pharmacology

Background:

  • Hypoxia, a state of low oxygen, is prevalent in solid tumors and often correlates with nitroreductase (NTR) overexpression.
  • NTR overexpression in tumors presents a therapeutic target for prodrug activation, enabling localized drug delivery and enhanced antitumor effects.

Purpose of the Study:

  • To develop novel evodiamine-based theranostic agents for hypoxia-targeting cancer therapy.
  • To enable simultaneous tumor imaging and therapeutic agent release through NTR-mediated activation.

Main Methods:

  • Design and synthesis of evodiamine-based prodrugs activated by nitroreductase (NTR).
  • Evaluation of selective NTR-mediated activation, fluorescence properties, and antitumor efficacy in vitro and in vivo.
  • Assessment of Probe-2's antitumor activity and toxicity in HCT116 xenograft nude mice.

Main Results:

  • The developed theranostic agents were selectively activated by NTR, showing excellent fluorescence and antitumor potency.
  • Probe-2 demonstrated significant in vivo antitumor activity with a tumor growth inhibition (TGI) of 76.1% in HCT116 xenografts.
  • The agents exhibited favorable tumor-targeting properties and low systemic toxicity.

Conclusions:

  • NTR-responsive theranostic agents offer a promising platform for hypoxia-targeted cancer treatment.
  • These agents facilitate prodrug activation, enabling simultaneous monitoring and therapeutic substance release.
  • Evodiamine-based theranostics show potential for enhancing antitumor efficacy in solid tumors with controlled drug release.