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Role of size, surface charge, and PEGylated lipids of lipid nanoparticles (LNPs) on intramuscular delivery of mRNA.
Kong, Weiwen; Wei, Yuning; Dong, Zirong; Liu, Wenjuan; Zhao, Jiaxin; Huang, Yan; Yang, Jinlong; Wu, Wei; He, Haisheng; Qi, Jianping.
Afiliación
  • Kong W; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, 201203, China.
  • Wei Y; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, 201203, China.
  • Dong Z; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, 201203, China.
  • Liu W; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, 201203, China.
  • Zhao J; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, 201203, China.
  • Huang Y; Department of Oncology, Shanghai Medical College of Fudan University, 270 Dong-an Road, Shanghai, 200032, China.
  • Yang J; Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, 270 Dong-an Road, Shanghai, 200032, China.
  • Wu W; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, 201203, China.
  • He H; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, 201203, China.
  • Qi J; School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Ministry of Education, Shanghai, 201203, China. he_haisheng@fudan.edu.cn.
J Nanobiotechnology ; 22(1): 553, 2024 Sep 11.
Article en En | MEDLINE | ID: mdl-39261807
ABSTRACT
Lipid nanoparticles (LNPs) are currently the most commonly used non-viral gene delivery system. Their physiochemical attributes, encompassing size, charge and surface modifications, significantly affect their behaviors both in vivo and in vitro. Nevertheless, the effects of these properties on the transfection and distribution of LNPs after intramuscular injection remain elusive. In this study, LNPs with varying sizes, lipid-based charges and PEGylated lipids were formulated to study their transfection and in vivo distribution. Luciferase mRNA (mLuc) was entraped in LNPs as a model nucleic acid molecule. Results indicated that smaller-sized LNPs and those with neutral potential presented superior transfection efficiency after intramuscular injection. Surprisingly, the sizes and charges did not exert a notable influence on the in vivo distribution of the LNPs. Furthermore, PEGylated lipids with shorter acyl chains contributed to enhanced transfection efficiency due to their superior cellular uptake and lysosomal escape capabilities. Notably, the mechanisms underlying cellular uptake differed among LNPs containing various types of PEGylated lipids, which was primarily attributed to the length of their acyl chain. Together, these insights underscore the pivotal role of nanoparticle characteristics and PEGylated lipids in the intramuscular route. This study not only fills crucial knowledge gaps but also provides significant directions for the effective delivery of mRNA via LNPs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tamaño de la Partícula / Polietilenglicoles / ARN Mensajero / Transfección / Nanopartículas / Lípidos Límite: Animals / Humans Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tamaño de la Partícula / Polietilenglicoles / ARN Mensajero / Transfección / Nanopartículas / Lípidos Límite: Animals / Humans Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido