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A Dual-Mechanism Targeted Cross-Convergence Prodrug Activation Strategy Enabled by Biological Stimulus Amplification
Zeyu Wang1, Yajie Xing1, Dong Wang1
1Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
Biomaterials Research
|May 22, 2026
Summary
This study introduces a novel dual-mechanism strategy for targeted cancer therapy. It combines tumor-specific prodrug delivery with amplified reactive oxygen species (ROS) for precise drug release and enhanced treatment efficacy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Current prodrug strategies face challenges in tumor targeting, systemic toxicity, and administration.
- Need for advanced drug delivery systems with improved specificity and efficacy.
Purpose of the Study:
- To develop a dual-mechanism targeted cross-convergence activation strategy for precision cancer therapy.
- To couple tumor-targeting prodrug delivery with biological stimulus amplification for controlled drug release.
Main Methods:
- Utilized BTW2 nanoparticles (ROS-responsive, biotin-conjugated) for tumor accumulation via EPR effect and biotin-receptor uptake.
- Employed IR-808 (heptamethine dye) for tumor targeting via organic-anion-transporting polypeptides and ROS amplification.
- Investigated the cross-convergence activation mechanism at tumor sites.
Main Results:
- IR-808 elevated ROS levels, triggering BTW2 nanoparticle activation and release of W436 (tubulin inhibitor).
- Released W436 further amplified ROS, creating a self-reinforcing positive feedback loop.
- Demonstrated spatiotemporally controlled and self-reinforcing drug release for effective cancer treatment.
Conclusions:
- The dual-mechanism strategy achieves precise and highly efficient drug release.
- This approach offers potential for precision therapy in primary and metastatic cancers.
- The self-reinforcing positive feedback loop enhances therapeutic outcomes.
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