Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.
Adv Mater. 2021 Dec;33(52):e2104355. doi: 10.1002/adma.202104355. Epub 2021 Oct 17.
Intracellular delivery of proteins is receiving considerable attention in biotherapeutics for various diseases by replacing dysfunctional proteins. Successful intracellular protein delivery highly relies on the development of efficient and safe polymeric carriers, which remains a grand challenge due to the lack of strong binding sites on proteins and their distinct molecular sizes and polarities. In this work, a strategy is proposed for efficient intracellular protein delivery by using dynamic polymer supra-amphiphiles, which are prepared by grafting boronated polylysine with a series of lipidated catechols via dynamic covalent catechol-boronate ester bonds. The prepared supra-amphiphiles can coassemble with proteins to form stable nanoparticles in water and also enable the release of bound proteins in cells due to their dynamic features, thereby strongly promoting the intracellular delivery process. The lead supra-amphiphiles screened in the library demonstrate high efficiency in the delivery of various proteins including bovine serum albumin, β-galactosidase, α-chymotrypsin, saporin, R-phycoerythrin, ovalbumin, catalase, and superoxide dismutase, and show great potency in delivering superoxide dismutase to treat ulcerative colitis in vivo. This work provides new opportunities for rational design and facile construction of robust intracellular protein delivery materials by the integration of polymer chemistry and supramolecular engineering strategies.
通过取代功能失调的蛋白质，将蛋白质递送到细胞内是治疗各种疾病的生物治疗中受到广泛关注的一种方法。成功的细胞内蛋白质递送高度依赖于高效和安全的聚合物载体的发展，由于蛋白质缺乏强结合位点以及它们独特的分子大小和极性，这仍然是一个巨大的挑战。在这项工作中，通过使用动态聚合物超两亲物来提出了一种有效的细胞内蛋白质递送策略，所述动态聚合物超两亲物是通过将硼化聚赖氨酸与一系列脂质化儿茶酚通过动态儿茶酚硼酸酯键接枝而制备的。所制备的超两亲物可以与蛋白质共组装在水中形成稳定的纳米颗粒，并且由于其动态特性，还可以在细胞中释放结合的蛋白质，从而强烈促进细胞内递送过程。在库中筛选出的先导超两亲物在递送各种蛋白质（包括牛血清白蛋白、β-半乳糖苷酶、α-糜蛋白酶、丝裂原、藻红蛋白、卵清蛋白、过氧化氢酶和超氧化物歧化酶）方面表现出高效率，并显示出在体内递送超氧化物歧化酶以治疗溃疡性结肠炎方面的巨大潜力。这项工作通过将聚合物化学和超分子工程策略相结合，为合理设计和简便构建稳健的细胞内蛋白质递送材料提供了新的机会。
