Develop Targeted Protein Drug Carriers through a High-Throughput Screening Platform and Rational Design.

Autor: Li X; Department of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, P. R. China.; Nanhu Brain-Computer Interface Institute, Hangzhou, 311100, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, 1369 West Wenyi Road, Hangzhou, 311121, China.; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, 310058, China., Zuo Y; Department of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, P. R. China.; Nanhu Brain-Computer Interface Institute, Hangzhou, 311100, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, 1369 West Wenyi Road, Hangzhou, 311121, China.; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, 310058, China., Lin X; Department of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, P. R. China.; Lingang Laboratory, Shanghai, 200031, China., Guo B; Department of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, P. R. China.; Lingang Laboratory, Shanghai, 200031, China., Jiang H; Department of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, P. R. China.; Lingang Laboratory, Shanghai, 200031, China., Guan N; Department of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, P. R. China.; Nanhu Brain-Computer Interface Institute, Hangzhou, 311100, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, 1369 West Wenyi Road, Hangzhou, 311121, China.; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, 310058, China., Zheng H; Department of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, P. R. China.; Lingang Laboratory, Shanghai, 200031, China., Huang Y; Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China., Gu X; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong, Jiangsu, 226001, P. R. China., Yu B; Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong, Jiangsu, 226001, P. R. China., Wang X; Department of Neurobiology and Department of Rehabilitation Medicine, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, P. R. China.; Nanhu Brain-Computer Interface Institute, Hangzhou, 311100, China.; Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, 1369 West Wenyi Road, Hangzhou, 311121, China.; NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, 310058, China.; Lingang Laboratory, Shanghai, 200031, China.; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, P. R. China.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2024 Nov; Vol. 13 (28), pp. e2401793. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1002/adhm.202401793
Abstrakt: Protein-based drugs offer advantages, such as high specificity, low toxicity, and minimal side effects compared to small molecule drugs. However, delivery of proteins to target tissues or cells remains challenging due to the instability, diverse structures, charges, and molecular weights of proteins. Polymers have emerged as a leading choice for designing effective protein delivery systems, but identifying a suitable polymer for a given protein is complicated by the complexity of both proteins and polymers. To address this challenge, a fluorescence-based high-throughput screening platform called ProMatch to efficiently collect data on protein-polymer interactions, followed by in vivo and in vitro experiments with rational design is developed. Using this approach to streamline polymer selection for targeted protein delivery, candidate polymers from commercially available options are identified and a polyhexamethylene biguanide (PHMB)-based system for delivering proteins to white adipose tissue as a treatment for obesity is developed. A branched polyethylenimine (bPEI)-based system for neuron-specific protein delivery to stimulate optic nerve regeneration is also developed. The high-throughput screening methodology expedites identification of promising polymer candidates for tissue-specific protein delivery systems, thereby providing a platform to develop innovative protein-based therapeutics.
(© 2024 Wiley‐VCH GmbH.)
Databáze: MEDLINE
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