Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation for Cancer Therapy

用于癌症治疗的热休克蛋白 90 (Hsp90) 抑制剂 Luminespib 负载蛋白质纳米制剂

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作者:Ankit K Rochani, Sivakumar Balasubramanian, Aswathy Ravindran Girija, Toru Maekawa, Gagan Kaushal, D Sakthi Kumar

Abstract

Drugs targeting heat shock protein 90 (Hsp90) have been extensively explored for their anticancer potential in advanced clinical trials. Nanoformulations have been an important drug delivery platform for the anticancer molecules like Hsp90 inhibitors. It has been reported that bovine serum albumin (BSA) nanoparticles (NPs) serve as carriers for anticancer drugs, which have been extensively explored for their therapeutic efficacy against cancers. Luminespib (also known as NVP-AUY922) is a new generation Hsp90 inhibitor that was introduced recently. It is one of the most studied Hsp90 inhibitors for a variety of cancers in Phase I and II clinical trials and is similar to its predecessors such as the ansamycin class of molecules. To our knowledge, nanoformulations for luminespib remain unexplored for their anticancer potential. In the present study, we developed aqueous dispensable BSA NPs for controlled delivery of luminespib. The luminespib-loaded BSA NPs were characterized by SEM, TEM, FTIR, XPS, UV-visible spectroscopy and fluorescence spectroscopy. The results suggest that luminespib interacts by non-covalent reversible interactions with BSA to form drug-loaded BSA NPs (DNPs). Our in vitro evaluations suggest that DNP-based aqueous nanoformulations can be used in both pancreatic (MIA PaCa-2) and breast (MCF-7) cancer therapy.

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