High‐dose vitamin D metabolite delivery inhibits breast cancer metastasis

作者：Jiaye Liu, Junyi Shen, Chunyang Mu, Yang Liu, Yang Liu, Dongsheng He, Han Luo, Wenshuang Wu, Xun Zheng, Yi Liu, Yi Liu, Sunrui Chen, Qiuwei Pan, Yiguo Hu, Yong Liu, Yang Wang, Yong Liu, Yong Liu, Zhihui Li · 发表于：Bioengineering & Translational Medicine · 年份：2021 · DOI：10.1002/btm2.10263 · 被引用次数：7 · 研究领域：Vitamin D Research Studies、Nanoparticle-Based Drug Delivery、Peptidase Inhibition and Analysis

, has been being evaluated in clinical trials as an anticancer agent. However, currently available results are contradictory and not fundamentally deciphered. To the best of our knowledge, hypercalcemia caused by high-dose calcitriol administration and its low bioavailability limit its anticancer investigations and translations. Here, we show that the one-step self-assembly of calcitriol and amphiphilic cholesterol-based conjugates leads to the formation of a stable minimalist micellar nanosystem. When administered to mice, this nanosystem demonstrates high calcitriol doses in breast tumor cells, significant tumor growth inhibition and antimetastasis capability, as well as good biocompatibility. We further reveal that the underlying molecular antimetastatic mechanisms involve downregulation of proteins facilitating metastasis and upregulation of paxillin, the key protein of focal adhesion, in primary tumors.