Asrorov Akmal M, Gu Zeyun, Min Kyoung Ah, Shin Meong Cheol, Huang Yongzhuo
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
Institute of Bioorganic Chemistry, Academy of Sciences of Uzbekistan, 83, M. Ulughbek Street, Tashkent 100125, Uzbekistan.
ACS Pharmacol Transl Sci. 2019 Dec 30;3(1):107-118. doi: 10.1021/acsptsci.9b00087. eCollection 2020 Feb 14.
Great attention has been paid to cytotoxic proteins (e.g., ribosome-inactivating proteins, RIPs) possessing high anticancer activities; unlike small drugs, cytotoxic proteins can effectively retain inside the cells and avoid drug efflux mediated by multidrug resistance transporters due to the large-size effect. However, the clinical translation of these proteins is severely limited because of various biobarriers that hamper their effective delivery to tumor cells. Hence, in order to overcome these barriers, many smart drug delivery systems (DDS) have been developed. In this review, we will introduce two representative type I RIPs, trichosanthin (TCS) and gelonin (Gel), and overview the major biobarriers for protein-based cancer therapy. Finally, we outline advances on the development of smart DDS for effective delivery of these cytotoxic proteins for various applications in cancer treatment.
具有高抗癌活性的细胞毒性蛋白（例如，核糖体失活蛋白，RIPs）已受到极大关注；与小分子药物不同，由于其大尺寸效应，细胞毒性蛋白可有效保留在细胞内，并避免由多药耐药转运蛋白介导的药物外排。然而，由于各种生物屏障阻碍其有效递送至肿瘤细胞，这些蛋白的临床转化受到严重限制。因此，为了克服这些障碍，已开发出许多智能药物递送系统（DDS）。在本综述中，我们将介绍两种代表性的I型RIPs，天花粉蛋白（TCS）和相思子毒素（Gel），并概述基于蛋白质的癌症治疗的主要生物屏障。最后，我们概述了用于有效递送这些细胞毒性蛋白以用于癌症治疗中各种应用的智能DDS的开发进展。
