ArticleAsian journal of pharmaceutical sciences2024
A natural compound-empowered podophyllotoxin prodrug nanoassembly magnifies efficacy-toxicity benefits in cancer chemotherapy.
Article in Asian journal of pharmaceutical sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- One-Stone-Two-Birds Carrier-Free Nano-Cocktail Enables Synergistic Eradication of Cancer Cells/Stem Cells in Breast Cancer Treatment.Exploration (Beijing, China) · 2026Article
- Reengineering glycyrrhetinic acid into a therapeutic oligomer for targeted tumor therapy with cardioprotection.Journal of nanobiotechnology · 2025Article
- Construction of a programmed activation nanosystem based on intracellular hypoxia in cisplatin-resistant tumor cells for reversing cisplatin resistance.Materials today. Bio · 2025Article
- The Potential of Nano-Formulated Natural Drugs in Melanoma Treatment: A Review of Pharmacological Efficacy and Mechanistic Insights.International journal of nanomedicine · 2025Review
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Authors and funding
9 authors.
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Abstract
Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery. However, prodrug activation remains a rate-limiting step for exerting therapeutic actions, which requires to quickly reach the minimum valid concentrations of free drugs. Fortunately, we find that a natural compound (BL-193) selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin (PPT) at ineffective dose concentrations. Based on this, we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT. Specifically, a redox-sensitive prodrug (PSSF) of PPT is synthesized by coupling 9-fluorenyl-methanol (Fmoc-OH) with PPT linked via disulfide bond. Intriguingly, PSSF with a π-conjugated structure readily co-assembles with BL-193 into stable nanoassembly. Significantly, BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic window for PPT. Moreover, prodrug design and precise hybrid nanoassembly well manage off-target toxicity. As expected, such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses. This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.
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