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Polymeric Nanocarriers with Controlled Chain Flexibility Boost mRNA Delivery In Vivo through Enhanced Structural Fastening
Author(s) -
Miyazaki Takuya,
Uchida Satoshi,
Nagatoishi Satoru,
Koji Kyoko,
Hong Taehun,
Fukushima Shigeto,
Tsumoto Kouhei,
Ishihara Kazuhiko,
Kataoka Kazunori,
Cabral Horacio
Publication year - 2020
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202000538
Subject(s) - nanocarriers , messenger rna , ethylene glycol , in vivo , micelle , peg ratio , biophysics , materials science , pegylation , polylysine , polymer , chemistry , nanotechnology , drug delivery , biochemistry , polyethylene glycol , biology , aqueous solution , organic chemistry , microbiology and biotechnology , finance , economics , gene , composite material
Messenger RNA (mRNA) shows high therapeutic potential, though effective delivery systems are still needed for boosting its application. Nanocarriers loading mRNA via polyion complexation with block catiomers into core‐shell micellar structures are promising systems for enhancing mRNA delivery. Engineering the interaction between mRNA and catiomers through polymer design can promote the development of mRNA‐loaded micelles (mRNA/m) with increased delivery efficiency. Particularly, the polycation chain rigidity may critically affect the mRNA‐catiomer interplay to yield potent nanocarriers, yet its effect remains unknown. Herein, the influence of polycation stiffness on the performance of mRNA/m by developing block complementary catiomers having polycation segments with different flexibility, that is, poly(ethylene glycol)‐poly(glycidylbutylamine) (PEG‐PGBA) and PEG‐poly(L‐lysine) (PEG‐PLL) is studied. PEG‐PGBA allows more than 50‐fold stronger binding to mRNA than the relatively more rigid PEG‐PLL, resulting in mRNA/m with enhanced protection against enzymatic attack and polyanions. mRNA/m from PEG‐PGBA significantly enhances mRNA in vivo bioavailability and increased protein translation, indicating the importance of controlling polycation flexibility for forming stable polyion complexes with mRNA toward improved delivery.