Genetically Engineered Nanoparticles of Asymmetric Triblock Polypeptide with a Platinum(IV) Cargo Outperforms a Platinum(II) Analog and Free Drug in a Murine Cancer Model.

Abstract

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 ∼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.

• Authors: Soumen Saha, Samagya Banskota, Jianqiao Liu, Nikita Zakharov, Michael Dzuricky, Xinghai Li, Ping Fan, Sonal Deshpande, Ivan Spasojevic, Kedar Sharma, Mario Juan Borgnia, Jeffrey L Schaal, Ashutosh Raman, Sarah Kim, Jayanta Bhattacharyya, Ashutosh Chilkoti
• Journal: Nano letters (Nano Lett) Vol. 22 Issue 14 Pg. 5898-5908 (07 27 2022) ISSN: 1530-6992 [Electronic] United States
• PMID: 35839459 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Peptides
• Prodrugs
• Platinum
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (chemistry, therapeutic use)
• Cell Line, Tumor
• Cisplatin (chemistry, therapeutic use)
• Mice
• Nanoparticles (chemistry)
• Neoplasms (drug therapy, genetics, pathology)
• Peptides (therapeutic use)
• Platinum (chemistry)
• Prodrugs (chemistry)