ArticleSmart molecules : open access2026
Redox-responsive dual-drug nanomedicine integrating cisplatin and trypsin for synergistic reversal of tumor chemoresistance.
Article in Smart molecules : open access, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors.
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Abstract
To overcome cisplatin resistance without increasing systemic toxicity, we rationally elaborated a glutathione-activatable prodrug nanomedicine that chemically co-encapsulates cisplatin and a masked protease. First, a redox-labile succinimide linker (NC-ss-COOH) was covalently grafted onto the ε-amino groups of trypsin to create a "pro-protease" (ssTrypsin) whose catalytic activity is completely silenced in circulation but instantly restored (≥96%) upon cleavage by intratumoral GSH. Simultaneously, cisplatin was stably coordinated to the carboxyl-rich backbone of cRGD-PEG-polyglutamic acid and carboxyl-rich ssTrypsin, forming a polymer-Pt(II) prodrug that prevents premature Pt-GSH adduct formation. These two prodrugs co-self-assemble into potent anti-tumor nanoconstructs that actively target α
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