Key result
Cisproplatin delivers superior anticancer potency vs cisplatin in TNBC cells with negligible toxicity in mice.
Why the study?
Cisplatin clinical utility is limited by severe nephrotoxicity and neurotoxicity.
Does cisproplatin improve antitumor efficacy and reduce toxicity compared to cisplatin in preclinical models?
Does cisproplatin improve antitumor efficacy and reduce toxicity compared to cisplatin in preclinical models?
Cisproplatin is a novel redox-activatable Pt(IV) conjugate that demonstrates superior anticancer potency and reduced dose-limiting toxicity compared to cisplatin in preclinical models.
Offers a hypothesis-generating strategy to mitigate dose-limiting platinum toxicities; leaves open.
Cisplatin's clinical utility is limited by severe nephrotoxicity and neurotoxicity. We developed cisproplatin (CPP), a Pt(IV) conjugate combining cisplatin and probenecid in a single, redox-activatable scaffold. CPP exhibits excellent stability under physiological, acidic pH and in serum, yet releases active components under reducing conditions. CPP displays superior potency across the NCI-60 panel, exceeding that of cisplatin. Time-resolved speciation and other physicochemical studies validate a dual mechanism, in which its Pt(IV) state interacts with DNA noncovalently, then releases cisplatin-like Pt(II) species upon reduction, yielding cumulative cytotoxicity. In TNBC cells, CPP outperforms cisplatin and cisplatin/probenecid mixtures, reducing the overall growth and proliferation. In BALB/c mice, CPP exhibited negligible toxicity with low neurotoxicity in CIPN model. Pharmacokinetic analysis showed reduced renal platinum accumulation and prolonged circulation. Together, these data establish CPP as a redox-activatable dual-drug Pt(IV) platform that decouples robust anticancer potency from classical dose-limiting toxicity.
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Kajol et al. (2026) studied Cancer. Cisproplatin (CPP) vs. Cisplatin and cisplatin/probenecid mixtures was evaluated on Anticancer potency and toxicity. Cisproplatin (CPP) demonstrated superior anticancer potency compared to cisplatin in TNBC cells and the NCI-60 panel, while exhibiting negligible toxicity and low neurotoxicity in mice.
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