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Exogenous/endogenous stimuli-responsive antitumor prodrugs advance precision chemotherapy

Luo Wang1, Jingao Li1, Xuanwei Zeng1

  • 1State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.

Bioorganic & Medicinal Chemistry
|November 18, 2025
PubMed

Insights

Stimuli-responsive prodrugs offer precision chemotherapy by using external or internal triggers to activate drugs only at tumor sites. This approach minimizes side effects and enhances treatment effectiveness for better cancer therapy.

Area of Science:

  • Oncology
  • Drug Delivery
  • Biomedical Engineering

Background:

  • Traditional chemotherapy faces challenges with off-target toxicity, affecting healthy cells.
  • Precision chemotherapy seeks to selectively target cancer cells, improving therapeutic outcomes.
  • Stimuli-responsive prodrugs represent a significant advancement, enabling targeted drug activation.

Purpose of the Study:

  • To review recent advances in stimuli-responsive antitumor prodrugs.
  • To analyze design principles, activation mechanisms, and therapeutic efficacy.
  • To highlight the potential of these prodrugs for enhanced cancer therapy.

Main Methods:

  • Analysis of exogenous stimuli-responsive prodrugs (light, radiation, ultrasound).
  • Analysis of endogenous stimuli-responsive prodrugs (hypoxia, pH, enzymes, ROS, GSH).
  • Focus on prodrug design, trigger mechanisms, and clinical efficacy.

Main Results:

  • Exogenous stimuli offer spatiotemporal precision for reduced systemic side effects.
  • Endogenous stimuli exploit the tumor microenvironment for selective drug activation.
  • Prodrugs undergo specific reactions to release active agents at target sites.

Conclusions:

  • Stimuli-responsive prodrugs enhance therapeutic efficacy and safety in cancer treatment.
  • These strategies pave the way for more precise and effective chemotherapy.
  • Targeted drug activation minimizes damage to healthy tissues, improving patient outcomes.
Keywords:
ChemotherapyOff-target toxicityProdrugsSide effectsStimuli-responsive

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