Selectively Inducing Cancer Cell Death by Intracellular Enzyme‐Instructed Self‐Assembly (EISA) of Dipeptide Derivatives

• DOI: 10.1002/adhm.201601400
• Publication Date: 2017-02-24T07:08:04Z
• Authors: Jie Li; Junfeng Shi; Jamie E. Medina; Jie Zhou; Xuewen Du; Huaimin Wang; Cuihong Yang; Jianfeng Liu; Zhimou Yang; Daniela M. Dinulescu; Bing Xu
• Keywords: 0301 basic medicine; 03 medical and health sciences; Treatment Outcome; Dose-Response Relationship, Drug; Cell Line, Tumor; Humans; Antineoplastic Agents; Apoptosis; Dipeptides; Neoplasms, Experimental; Carboxylic Ester Hydrolases; 3. Good health

Tight ligand‐receptor binding, paradoxically, is a major root of drug resistance in cancer chemotherapy. To address this problem, instead using conventional inhibitors or ligands, paper focuses on the development novel process—enzyme‐instructed self‐assembly (EISA)—to kill cells selectively. Here it demonstrated that EISA as an intracellular process to generate nanofibrils short peptides for selectively inhibiting cell proliferation, including resistant ones. As turns non‐self‐assembling precursors into self‐assembling upon catalysis carboxylesterases (CES), occurs intracellularly inhibit range exhibit relatively high CES activities. More importantly, inhibits (e.g., triple negative breast (HCC1937) and platinum‐resistant ovarian (SKOV3, A2780cis)). With IC 50 values 28–80 25–44 µg mL −1 l ‐ d ‐dipeptide against cells, respectively, innocuous normal cells. Moreover, coculture selectivity validated Besides revealing cause apoptosis necroptosis work illustrates new approach amplify enzymatic difference between expand pool candidates potentially overcoming therapy.