South China Advanced Institute for Soft Matter Science and Technology, School of Molecular Science and Engineering, South China University of Technology, Guangzhou, 510640, P. R. China.
Department of Orthopedics Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, P. R. China.
Small. 2020 Dec;16(49):e2004829. doi: 10.1002/smll.202004829. Epub 2020 Nov 17.
Numerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs; however, the complexities in carrier materials and functional integration make it challenging to promote these candidates for clinical translation. In this study, a facile method to prepare carrier-free anticancer nanodrug with inherent bone targeting and osteoclastogenesis inhibition capabilities is reported. Phytic acid, a naturally occurring and nontoxic product, is reacted with cisplatin to form uniform nanoparticles of different sizes. The prepared nanoparticles possess high drug loading and pH-responsive drug release behaviors. Phytic acid in the nanomedicine ensures high bone targeting and osteoclastogenesis inhibition, and the released platinum drugs triggered by tumor extracellular acidity eradicate tumor cells. The nanomedicine around 100 nm shows high anticancer activity and much reduced side effects in a subcutaneous breast cancer model when compared with cisplatin. In addition, it shows high accumulation at osteolytic lesions, and efficiently inhibits tumor growth and tumor-associated osteolysis in a bone metastatic breast cancer model. Here, a facile and efficient strategy to prepare carrier-free nanomedicines with high anticancer drug loading, inherent bone targeting, and osteoclast inhibitory activities for cancer therapy is provided.
已经开发出许多纳米药物来提高传统抗癌药物的效率和安全性;然而,载体材料的复杂性和功能集成使得这些候选药物难以推广用于临床转化。在这项研究中,报道了一种简便的方法来制备具有内在骨靶向和破骨细胞抑制能力的无载体抗癌纳米药物。植酸是一种天然存在且无毒的产物,与顺铂反应形成不同大小的均匀纳米颗粒。所制备的纳米颗粒具有高药物负载和 pH 响应性药物释放行为。纳米药物中的植酸确保了高骨靶向性和破骨细胞抑制作用,而由肿瘤细胞外酸度引发的释放的铂类药物则可以消灭肿瘤细胞。与顺铂相比,粒径约为 100nm 的纳米药物在皮下乳腺癌模型中表现出更高的抗癌活性和更低的副作用。此外,它在溶骨性病变部位有很高的蓄积,在骨转移乳腺癌模型中能有效抑制肿瘤生长和肿瘤相关骨溶解。这里提供了一种简便有效的策略来制备具有高抗癌药物负载、内在骨靶向和破骨细胞抑制活性的无载体纳米药物,用于癌症治疗。