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Your search keyword '"Toyoda, Masahiro"' showing total 312 results
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312 results on '"Toyoda, Masahiro"'

6. Fine tuning of the net charge alternation of polyzwitterion surfaced lipid nanoparticles to enhance cellular uptake and membrane fusion potential.

Author

Homma, Keitaro, Miura, Yutaka, Kobayashi, Motoaki, Chintrakulchai, Wanphiwat, Toyoda, Masahiro, Ogi, Koichi, Michinishi, Junya, Ohtake, Tomoyuki, Honda, Yuto, Nomoto, Takahiro, Takemoto, Hiroyasu, and Nishiyama, Nobuhiro

Subjects
SMALL interfering RNA, MEMBRANE fusion, MESSENGER RNA, ETHYLENE glycol, GENE silencing, ZWITTERIONS
Abstract

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. IMPACT STATEMENT: The study presents the unique characteristics of small interfering RNA (siRNA)-loaded lipid nanoparticles (LNPs) with different lengths of PGlu(DET-Car), revealing the length of PGlu(DET-Car) critically affects the formation of a stable LNP, the cellular uptake, membrane fusion, and gene silencing abilities. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Cancerous pH‐responsive polycarboxybetaine‐coated lipid nanoparticle for smart delivery of siRNA against subcutaneous tumor model in mice.

Author

Sung, Yi‐Jung, Guo, Haochen, Ghasemizadeh, Aria, Shen, Xin, Chintrakulchai, Wanphiwat, Kobayashi, Motoaki, Toyoda, Masahiro, Ogi, Koichi, Michinishi, Junya, Ohtake, Tomoyuki, Matsui, Makoto, Honda, Yuto, Nomoto, Takahiro, Takemoto, Hiroyasu, Miura, Yutaka, and Nishiyama, Nobuhiro

Abstract

Lipid nanoparticles (LNPs) have been commonly used as a vehicle for nucleic acids, such as small interfering RNA (siRNA); the surface modification of LNPs is one of the determinants of their delivery efficiency especially in systemic administration. However, the applications of siRNA‐encapsulated LNPs are limited due to a lack effective systems to deliver to solid tumors. Here, we report a smart surface modification using a charge‐switchable ethylenediamine‐based polycarboxybetaine for enhancing tumor accumulation via interaction with anionic tumorous tissue constituents due to selective switching to cationic charge in response to cancerous acidic pH. Our polycarboxybetaine‐modified LNP could enhance cellular uptake in cancerous pH, resulting in facilitated endosomal escape and gene knockdown efficiency. After systemic administration, the polycarboxybetaine‐modified LNP accomplished high tumor accumulation in SKOV3‐luc and CT 26 subcutaneous tumor models. The siPLK‐1‐encapsulated LNP thereby accomplished significant tumor growth inhibition. This study demonstrates a promising potential of the pH‐responsive polycarboxybetaine as a material for modifying the surface of LNPs for efficient nucleic acid delivery. [ABSTRACT FROM AUTHOR]

Published
2022
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