文献类型：期刊文献

英文题名：Redox-responsive peptide-based complex coacervates as delivery vehicles with controlled release of proteinous drugs

作者：Wang, Jiahua[1];Abbas, Manzar[2,3];Huang, Yu[1];Wang, Junyou[4,5];Li, Yuehua[1]

机构：[1]Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Sch Med, Dept Radiol, Shanghai 200233, Peoples R China;[2]Khalifa Univ Sci & Technol, Dept Chem, POB 127788, Abu Dhabi, U Arab Emirates;[3]Khalifa Univ Sci & Technol, Adv Mat Chem Ctr AMCC, POB 127788, Abu Dhabi, U Arab Emirates;[4]East China Univ Sci & Technol, State Key Lab Chem Engn, Shanghai 200237, Peoples R China;[5]East China Univ Sci & Technol, Shanghai Key Lab Multiphase Mat Chem Engn, Shanghai 200237, Peoples R China

年份：2023

卷号：6

期号：1

外文期刊名：COMMUNICATIONS CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001121033400002)】；

基金：This work was supported financially by the Fundamental Research Funds for the Shanghai Sixth People's Hospital (X-2430 to J.W.; X-2362 and ynqn202111 to Y.H.). This work was also supported by the Innovative Research Team of High-Level Local Universities in Shanghai. The authors also acknowledge the sponsorship from the National Natural Science Foundation of China (22205137 to Y.H.) and the Shanghai Pujiang Program (21PJ1411700 to Y.H.). M.A. acknowledges the financial support (Project No. 8474000462) from Khalifa University of Science and Technology, UAE.

语种：英文

摘要：Proteinous drugs are highly promising therapeutics to treat various diseases. However, they suffer from limited circulation times and severe off-target side effects. Inspired by active membraneless organelles capable of dynamic recruitment and releasing of specific proteins, here, we present the design of coacervates as therapeutic protocells, made from small metabolites (anionic molecules) and simple arginine-rich peptides (cationic motif) through liquid-liquid phase separation. These complex coacervates demonstrate that their assembly and disassembly can be regulated by redox chemistry, which helps to control the release of the therapeutic protein. A model proteinous drugs, tissue plasminogen activator (tPA), can rapidly compartmentalize inside the complex coacervates, and the coacervates formed from peptides conjugated with arginine-glycine-aspartic acid (RGD) motif (a fibrinogen-derived peptide sequence), show selective binding to the thrombus site and thus enhance on-target efficacy of tPA. Furthermore, the burst release of tPA can be controlled by the redox-induced dissolution of the coacervates. Our proof-of-principle complex coacervate system provides insights into the sequestration and release of proteinous drugs from advanced drug delivery systems and represents a step toward the construction of synthetic therapeutic protocells for biomedical applications. Therapeutic proteins have great potential for the treatment of various diseases, however, achieving high delivery efficiency remains challenging. Here, the authors develop a complex coacervate system formed via the phase separation of anionic metabolite NADPH with a short arginine-rich peptide, and apply it to the redox-responsive drug delivery of therapeutic proteins.