Mechanistic insights into interactions between ionizable lipid nanodroplets and biomembranes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F25%3A73625003" target="_blank" >RIV/61989592:15640/25:73625003 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989100:27740/25:10254766

Výsledek na webu

<a href="https://www.tandfonline.com/doi/full/10.1080/07391102.2024.2329307" target="_blank" >https://www.tandfonline.com/doi/full/10.1080/07391102.2024.2329307</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2024.2329307" target="_blank" >10.1080/07391102.2024.2329307</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mechanistic insights into interactions between ionizable lipid nanodroplets and biomembranes

Popis výsledku v původním jazyce

Delivery of RNA into cells using lipid nanoparticles (LNPs) has been a significant breakthrough in RNA-based medicine, with clinical applicability expanded through the use of ionizable lipids (ILs). These unique lipids can alter their charge state in response to pH changes, which is crucial for pH-triggered endosomal escape and effective lipid-mediated RNA delivery. In this study, we conducted a comprehensive set of molecular dynamics (MD) simulations to investigate interactions between IL-containing lipid nanodroplets (LNDs) and cell membrane models. Using an atomistic resolution model, we investigated the merging process of LNDs with cell membrane models under neutral conditions relevant to an intercellular environment and acidic pH conditions found in late endosomes. Our observations revealed that at neutral pH, LNDs merged with lipid membranes while preserving the bilayer structure. Under acidic conditions, the LNDs remained attached to the bilayer without fusing into the membranes. Importantly, the presence of ILs did not disrupt the original biomembrane structure during the simulation period. The MD simulations provided valuable atomistic insights into the mechanism of interaction between IL-containing nanodroplets and biomembranes, which could aid the rational design of ILs to develop more efficient LNPs for RNA therapies.

Název v anglickém jazyce

Mechanistic insights into interactions between ionizable lipid nanodroplets and biomembranes

Popis výsledku anglicky

Delivery of RNA into cells using lipid nanoparticles (LNPs) has been a significant breakthrough in RNA-based medicine, with clinical applicability expanded through the use of ionizable lipids (ILs). These unique lipids can alter their charge state in response to pH changes, which is crucial for pH-triggered endosomal escape and effective lipid-mediated RNA delivery. In this study, we conducted a comprehensive set of molecular dynamics (MD) simulations to investigate interactions between IL-containing lipid nanodroplets (LNDs) and cell membrane models. Using an atomistic resolution model, we investigated the merging process of LNDs with cell membrane models under neutral conditions relevant to an intercellular environment and acidic pH conditions found in late endosomes. Our observations revealed that at neutral pH, LNDs merged with lipid membranes while preserving the bilayer structure. Under acidic conditions, the LNDs remained attached to the bilayer without fusing into the membranes. Importantly, the presence of ILs did not disrupt the original biomembrane structure during the simulation period. The MD simulations provided valuable atomistic insights into the mechanism of interaction between IL-containing nanodroplets and biomembranes, which could aid the rational design of ILs to develop more efficient LNPs for RNA therapies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/EH22_008%2F0004587" target="_blank" >EH22_008/0004587: Technologie za hranicí nanosvěta</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

JOURNAL OF BIOMOLECULAR STRUCTURE &amp; DYNAMICS

ISSN

0739-1102

e-ISSN

1538-0254

Svazek periodika

43

Číslo periodika v rámci svazku

17

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

nestránkováno

Kód UT WoS článku

001185421500001

EID výsledku v databázi Scopus

2-s2.0-85188468956