Journal
BIOMATERIALS
Volume 182, Issue -, Pages 167-175Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.08.023
Keywords
Dendrimers; Fluoropolymer; Intracellular protein delivery; Peptides; Self-assembly
Funding
- National Natural Science Foundation of China [21725402, 20174030]
- Shanghai Municipal Science and Technology Commission [17XD1401600]
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The design of efficient and universal carriers to transport proteins into cells is highly desirable in the development of biotherapeutics. However, intracellular protein delivery remains a major challenge owing to the multiple barriers in protein delivery process, such as protein encapsulation, endocytosis, endosomal escape and intracellular protein release. Recently, it was reported that fluorination on polymers is beneficial for their selfassembly and intracellular trafficking. We hypothesize the fluoropolymers can be used to encapsulate proteins and developed as a new class of carriers to break down the barriers during intracellular protein delivery. In this study, we successfully discovered an efficient and non-toxic polymer for protein delivery in a library of fluoropolymers. The lead material A6-2 in the library efficiently transported various proteins including bovine serum albumin, beta-galactosidase, saporin and a cyclic hendecapeptide into the cytosol of living cells with minimal cytotoxicity. More importantly, activities of delivered proteins and peptides were maintained after delivery. The A6-2/saporin complex was further coated with a hyaluronic acid shell, and the yielding nanoparticle efficiently suppressed tumor growth in a breast cancer model by targeted protein delivery. This study provides a new insight into the design of efficient and biocompatible polymers for protein delivery.
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