Polymeric Nanocarriers with Controlled Chain Flexibility Boost mRNA Delivery In Vivo through Enhanced Structural Fastening

• DOI: 10.1002/adhm.202000538
• Publication Date: 2020-06-25T08:30:08Z
• Authors: Takuya Miyazaki; Satoshi Uchida; Satoru Nagatoishi; Kyoko Koji; Taehun Hong; Shigeto Fukushima; Kouhei Tsumoto; Kazuhiko Ishihara; Kazunori Kataoka; Horacio Cabral
• Keywords: Nanocarriers; Chain (unit)

Abstract 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 promising enhancing delivery. Engineering the interaction between and through polymer design can promote development of mRNA‐loaded micelles (mRNA/m) increased efficiency. Particularly, polycation chain rigidity may critically affect mRNA‐catiomer interplay to yield potent nanocarriers, yet effect remains unknown. Herein, influence stiffness on performance mRNA/m by developing complementary having segments different flexibility, that is, poly(ethylene glycol)‐poly(glycidylbutylamine) (PEG‐PGBA) PEG‐poly(L‐lysine) (PEG‐PLL) is studied. PEG‐PGBA allows more than 50‐fold stronger binding relatively rigid PEG‐PLL, resulting in enhanced protection against enzymatic attack polyanions. from significantly enhances vivo bioavailability protein translation, indicating importance controlling flexibility forming stable complexes toward improved