Advances on Tumor-Targeting Delivery of Cytotoxic Proteins

Akmal M Asrorov; Zeyun Gu; Kyoung Ah Min; Meong Cheol Shin; Yongzhuo Huang

doi:10.1021/acsptsci.9b00087

Advances on Tumor-Targeting Delivery of Cytotoxic Proteins

ACS Pharmacol Transl Sci. 2019 Dec 30;3(1):107-118. doi: 10.1021/acsptsci.9b00087. eCollection 2020 Feb 14.

Authors

Akmal M Asrorov^{1

2}, Zeyun Gu¹, Kyoung Ah Min³, Meong Cheol Shin⁴, Yongzhuo Huang¹

Affiliations

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
² Institute of Bioorganic Chemistry, Academy of Sciences of Uzbekistan, 83, M. Ulughbek Street, Tashkent 100125, Uzbekistan.
³ College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae, Gyeongnam 50834, Korea.
⁴ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju, Gyeongnam 52828, Korea.

Abstract

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.

Publication types

Review