Hatami Elham, Bhusetty Nagesh Prashanth Kumar, Chowdhury Pallabita, Elliot Stacie, Shields Deanna, Chand Chauhan Subhash, Jaggi Meena, Yallapu Murali Mohan
Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison Avenue, Memphis, Tennessee 38163, United States.
ACS Biomater Sci Eng. 2019 May 13;5(5):2343-2354. doi: 10.1021/acsbiomaterials.9b00362. Epub 2019 Apr 8.
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.
大多数癌症患者会发生骨转移，这会影响生活质量并显著降低生存率。积极的化疗是一种会引发严重全身毒性的传统治疗方案。因此，骨靶向治疗非常必要。我们报道了一种新型纳米颗粒制剂，它由聚乙烯吡咯烷酮和单宁酸核心纳米颗粒（PVT NPs）组成，并与唑来膦酸形成自组装体（ZA@PVT NPs）。通过粒径、zeta电位、透射电子显微镜和光谱分析证实了ZA@PVT NPs的结构。优化后的骨靶向ZA@PVT NPs制剂在体外对转移性前列腺癌细胞和乳腺癌细胞表现出更强的结合和内化能力。ZA@PVT NPs能够更有效地将ZA递送至肿瘤细胞，从而抑制人前列腺癌细胞和乳腺癌细胞的增殖。此外，ZA@PVT NPs能够靶向小鼠骨骼和前列腺肿瘤微阵列组织（体外），同时不会影响其他重要器官。更重要的是，ZA@PVT NPs能诱导癌细胞对多西他赛治疗产生化疗增敏作用。总体而言，研究结果证实基于ZA的骨靶向纳米颗粒在不久将来治疗骨转移方面具有巨大潜力。
