Journal
NANO LETTERS
Volume 22, Issue 14, Pages 5898-5908Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c01850
Keywords
Platinum II vs Platinum IV; biomimetic materials; block polypeptides; nanomedicine; cancer
Categories
Funding
- National Institutes of Health (MIRA) [R35GM127042]
- Dr. Reddy's laboratory, India
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Loading Pt(IV) into genetically engineered nanoparticles can enhance the therapeutic efficacy of platinum drugs, potentially yielding more effective platinum-drug nanoformulations.
The development of platinum(Pt)-drugs for cancer therapy has stalled, as no new Pt-drugs have been approved in over a decade. Packaging small molecule drugs into nanoparticles is a way to enhance their therapeutic efficacy. To date, there has been no direct comparison of relative merits of the choice of Pt oxidation state in the same nanoparticle system that would allow its optimal design. To address this lacuna, we designed a recombinant asymmetric triblock polypeptide (ATBP) that self-assembles into rod-shaped micelles and chelates Pt(II) or enables covalent conjugation of Pt(IV) with similar morphology and stability. Both ATBP-Pt(II) and ATBP-Pt(IV) nanoparticles enhanced the half-life of Pt by & SIM;45-fold, but ATBP-Pt(IV) had superior tumor regression efficacy compared to ATBP-Pt(II) and cisplatin. These results suggest loading Pt(IV) into genetically engineered nanoparticles may yield a new generation of more effective platinum-drug nanoformulations.
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