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In this study, a library of 144 functional triblock polymers using ring\u2010opening polymerization (ROP) and thiol\u2010ene click reaction is constructed. These triblock polymers are composed of hydrophilic poly (ethylene oxide) (PEO), hydrophobic poly (<jats:italic>\u03b5<\/jats:italic>\u2010caprolactone) (PCL), and cationic amine blocks. Three effective carriers are discovered by high\u2010throughput screening of these polymers for siRNA delivery to HeLa\u2010Luc cells. In vitro evaluation shows that siLuc\u2010loaded nanoparticles (NPs) fabricated with leading polymer carriers exhibit sufficient knockdown of luciferase genes and relatively low cytotoxicity. The chemical structure of polymers significantly affects the physicochemical properties of the resulting siRNA\u2010loaded NPs, which leads to different cellular uptake of NPs and endosomal escape of loaded siRNA and thus the overall in vitro siRNA delivery efficacy. After systemic administration to mice with xenograft tumors, siRNA NPs based on P2\u20104.5A8 are substantially accumulated at tumor sites, suggesting that PEO and PCL blocks are beneficial for improving blood circulation and biodistribution of siRNA NPs. This functional triblock polymer platform may have great potential in the development of siRNA\u2010based therapies for the treatment of cancers.<\/jats:p>","DOI":"10.1002\/mabi.202200232","type":"journal-article","created":{"date-parts":[[2022,9,10]],"date-time":"2022-09-10T07:05:24Z","timestamp":1662793524000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Construction of Degradable and Amphiphilic Triblock Polymer Carriers for Effective Delivery of siRNA"],"prefix":"10.1002","volume":"22","author":[{"given":"Yunfeng","family":"Yan","sequence":"first","affiliation":[{"name":"College of Biotechnology and Bioengineering Zhejiang University of Technology  Hangzhou Zhejiang 310014 P. R. 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