Type Of Media：学術論文
Publication/Magazine/Media：Science and Technology of Advanced Materials
Author：Keitaro Homma, Yutaka Miura, Motoaki Kobayashi, Wanphiwat Chintrakulchai, Masahiro Toyoda, Koichi Ogi, Junya Michinishi, Tomoyuki Ohtake, Yuto Honda, Takahiro Nomoto, Hiroyasu Takemoto and Nobuhiro Nishiyama
Fine tuning of the net charge alternation of polyzwitterion surfaced lipid nanoparticles to enhance cellular uptake and membrane fusion potential
Lipid nanoparticles (LNPs) coated with functional and biocompatible polymers have been widely used as carriers to deliver oligonucleotide and messenger RNA therapeutics to treat diseases. Poly(ethylene glycol) (PEG) is a representative material used for the surface coating, but the PEG surface-coated LNPs often have reduced cellular uptake efficiency and pharmacological activity. Here, we demonstrate the effect of pH-responsive ethylenediamine-based polycarboxybetaines with different molecular weights as an alternative structural component to PEG for the coating of LNPs. We found that appropriate tuning of the molecular weight around polycarboxybetaine-modified LNP, which incorporated small interfering RNA, could enhance the cellular uptake and membrane fusion potential in cancerous pH condition, thereby facilitating the gene silencing effect. This study demonstrates the importance of the design and molecular length of polymers on the LNP surface to provide effective drug delivery to cancer cells.
http://doi.org/10.1080/14686996.2024.2338785
