Transition Temperature-Guided Design of Lipid Nanoparticles for Effective mRNA Delivery DOI Creative Commons
Jeongeun Shin, Eun-Jeong Won, Junchao Xu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Lipid nanoparticles (LNPs) are promising mRNA delivery vehicles due to their biocompatibility and tunable characteristics. While current rational design approaches focus on ionizable lipids' pKa zeta potential optimize encapsulation endosomal escape, the selection of helper lipids remains largely empirical. We propose that lipid transition temperature (Tm), marking shift from gel liquid crystalline phase, can guide selection. Through screening 54 lipids, we identified H7T4, which displayed favorable physicochemical properties when combined with its tail variants but exhibited poor transfection efficiency. Using nano differential scanning calorimetry (nDSC) biological small-angle X-ray scattering (BioSAXS), found lowering system's Tm by combining H7T4 (high temperature) a low-transition-temperature such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) significantly enhanced cellular uptake both in vitro vivo. These findings establish crucial parameter for LNP design.

Language: Английский

Transition Temperature-Guided Design of Lipid Nanoparticles for Effective mRNA Delivery DOI Creative Commons
Jeongeun Shin, Eun-Jeong Won, Junchao Xu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: May 5, 2025

Lipid nanoparticles (LNPs) are promising mRNA delivery vehicles due to their biocompatibility and tunable characteristics. While current rational design approaches focus on ionizable lipids' pKa zeta potential optimize encapsulation endosomal escape, the selection of helper lipids remains largely empirical. We propose that lipid transition temperature (Tm), marking shift from gel liquid crystalline phase, can guide selection. Through screening 54 lipids, we identified H7T4, which displayed favorable physicochemical properties when combined with its tail variants but exhibited poor transfection efficiency. Using nano differential scanning calorimetry (nDSC) biological small-angle X-ray scattering (BioSAXS), found lowering system's Tm by combining H7T4 (high temperature) a low-transition-temperature such as 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) significantly enhanced cellular uptake both in vitro vivo. These findings establish crucial parameter for LNP design.

Language: Английский

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