Development of Zoledronic Acid-Based Nanoassemblies for Bone-Targeted Anticancer Therapy.

Abstract

Bone metastasis occurs in the majority of cancer patients, which hampers quality of life and significantly decreases survival. Aggressive chemotherapy is a traditional treatment regimen that induces severe systemic toxicities. Therefore, bone-directed therapies are highly warranted. We report a novel nanoparticle formulation that is composed of poly(vinylpyrrolidone) and tannic acid core nanoparticles (PVT NPs) that forms self-assembly with zoledronic acid (ZA@PVT NPs). The construction of ZA@PVT NPs was confirmed by particle size, zeta potential, transmission electron microscopy, and spectral analyses. An optimized bone-targeted ZA@PVT NPs formulation showed greater binding and internalization in in vitro with metastasis prostate and breast cancer cells. ZA@PVT NPs were able to deliver ZA more efficiently to tumor cells, which inhibited proliferation of human prostate and breast cancer cells. In addition, ZA@PVT NPs were capable of targeting mouse bones and prostate tumor microarray tissues (ex vivo) while sparing all other vital organs. More importantly, ZA@PVT NPs induce chemo sensitization to docetaxel treatment in cancer cells. Overall, the study results confirm that ZA-based, bone-targeted NPs have great potential for the treatment of bone metastasis in the near future.

• Authors: Elham Hatami, Prashanth Kumar Bhusetty Nagesh, Pallabita Chowdhury, Stacie Elliot, Deanna Shields, Subhash Chand Chauhan, Meena Jaggi, Murali Mohan Yallapu
• Journal: ACS biomaterials science & engineering (ACS Biomater Sci Eng) Vol. 5 Issue 5 Pg. 2343-2354 (May 13 2019) ISSN: 2373-9878 [Electronic] United States
• PMID: 33405784 (Publication Type: Journal Article)