Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center of Chemical Science and Engineering, and National Institute of Functional Materials, Nankai University, Tianjin 300071, P. R. China.
Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, 221004, P. R. China.
Nanoscale. 2019 Aug 7;11(29):13714-13719. doi: 10.1039/c9nr04262h. Epub 2019 Jul 17.
The selective formation of nanomedicines around cancer cells is very important for cancer therapy because it increases the inhibitory capacity and decreases the systemic toxicity. However, successful examples are rare. Taking advantage of the overexpression of both the enzyme alkaline phosphatase (ALP) and the cell membrane receptor (CCK2R), we demonstrated in this study the selective formation of supramolecular nanofibers and hydrogels in the pericellular space of two cancer cell lines (HeLa and HepG2 cells). Both cell lines showed high expression levels of extracellular ALP and membrane-bound CCK2R. ALP efficiently converted Comp. 1 to a self-assembling molecule (Comp. 2). Comp. 2 interacted with CCK2R, thereby facilitating the self-assembly and formation of hydrogels around the cancer cells. The selective pericellular hydrogelations efficiently inhibited cancer cells. Pericellular hydrogelation around cancer cells is a promising strategy to control the formation of nanomedicines spatiotemporally in cellular microenvironments for cancer therapy and diagnostics.
在癌细胞周围选择性地形成纳米药物对于癌症治疗非常重要，因为它可以提高抑制能力并降低系统毒性。然而，成功的例子很少。本研究利用碱性磷酸酶（ALP）酶和细胞膜受体（CCK2R）的过度表达，在两种癌细胞系（HeLa 和 HepG2 细胞）的细胞外空间中证明了超分子纳米纤维和水凝胶的选择性形成。两种细胞系均表现出高水平的细胞外 ALP 和膜结合的 CCK2R。ALP 有效地将 Comp. 1 转化为自组装分子（Comp. 2）。Comp. 2 与 CCK2R 相互作用，从而促进水凝胶在癌细胞周围的自组装和形成。选择性的细胞周围水凝胶化有效地抑制了癌细胞。癌细胞周围的细胞周围水凝胶化是一种很有前途的策略，可以控制纳米药物在细胞微环境中的时空形成，用于癌症治疗和诊断。
