Department of Chemistry, City University of Hong Kong, 83 Tat Chee Ave, Kowloon Tong, Hong Kong SAR, P. R. China.
City University of Hong Kong Shenzhen Research Institute, Shenzhen, P. R. China.
Angew Chem Int Ed Engl. 2018 Mar 19;57(13):3426-3430. doi: 10.1002/anie.201800422. Epub 2018 Feb 27.
The efficacy of conventional chemotherapy is hindered by cancer cell escape from the immune system. A multifunctional nanohybrid system is reported for effective immunochemotherapy against cervical cancer. This nanohybrid contains both immune checkpoint inhibitor and cisplatin anticancer prodrug, showing improved cellular accumulation and increased binding of Pt to DNA and resulting in elevated apoptosis than using cisplatin alone when tested in cervical cancer cells. The immune checkpoint inhibitor enables the inhibition of indoleamine-2,3-dioxygenase and reverses immunosuppressive T cells to recognize cancer cells, leading to T cell proliferation and activation, cancer cell cycle arrest, and ultimately increased cancer cell death. The nanohybrid is also active in vivo against the growth of human cervical tumors. Overall, a strategy is provided using a multifunctional nanohybrid system to boost the antitumor activity of cisplatin.
常规化疗的疗效受到癌细胞逃避免疫系统的限制。本文报道了一种多功能纳米杂化系统，可有效进行宫颈癌的免疫化疗。该纳米杂化系统同时包含免疫检查点抑制剂和顺铂抗癌前药，在宫颈癌细胞中进行测试时，与单独使用顺铂相比，其具有改善的细胞积累和增加的 Pt 与 DNA 的结合，从而导致细胞凋亡增加。免疫检查点抑制剂能够抑制吲哚胺 2,3-双加氧酶并使抑制性 T 细胞逆转以识别癌细胞，导致 T 细胞增殖和激活、癌细胞周期停滞，最终增加癌细胞死亡。该纳米杂化系统在体内也能有效抑制人宫颈癌肿瘤的生长。总之，本文提供了一种使用多功能纳米杂化系统来增强顺铂抗肿瘤活性的策略。
