Dual Effect by Chemical Electron Transfer Enhanced siRNA Lipid Nanoparticles: Reactive Oxygen Species-Triggered Tumor Cell Killing Aggravated by Nrf2 Gene Silencing DOI Creative Commons
Fengrong Zhang, Tobias Burghardt,

Miriam Höhn

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(6), P. 779 - 779

Published: June 7, 2024

Insufficient endosomal escape presents a major hurdle for successful nucleic acid therapy. Here, the first time, chemical electron transfer (CET) system was integrated into small interfering RNA (siRNA) lipid nanoparticles (LNPs). The CET acceptor can be chemically excited using generated energy between donor and hydrogen peroxide, which triggers generation of reactive oxygen species (ROS), promoting membrane destabilization. Tetra-oleoyl tri-lysino succinoyl tetraethylene pentamine included as an ionizable lipopeptide with U-shaped topology effective siRNA encapsulation pH-induced escape. LNPs loaded components demonstrated more efficient escape, evidenced by galectin-8-mRuby reporter; ROS significantly augmented galectin-8 recruitment at least threefold compared control groups,

Language: Английский

Strategies and mechanisms for endosomal escape of therapeutic nucleic acids DOI Creative Commons

Melina Grau,

Ernst Wagner

Current Opinion in Chemical Biology, Journal Year: 2024, Volume and Issue: 81, P. 102506 - 102506

Published: Aug. 1, 2024

Despite impressive recent establishment of therapeutic nucleic acids as drugs and vaccines, their broader medical use is impaired by modest performance in intracellular delivery. Inefficient endosomal escape presents a major limitation responsible for inadequate cytosolic cargo release. Depending on the carrier, this barrier can strongly limit or even abolish acid Different strategies hypothesized mechanisms are reviewed.

Language: Английский

Citations

10
Dual Effect by Chemical Electron Transfer Enhanced siRNA Lipid Nanoparticles: Reactive Oxygen Species-Triggered Tumor Cell Killing Aggravated by Nrf2 Gene Silencing DOI Creative Commons
Fengrong Zhang, Tobias Burghardt,

Miriam Höhn

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(6), P. 779 - 779

Published: June 7, 2024

Insufficient endosomal escape presents a major hurdle for successful nucleic acid therapy. Here, the first time, chemical electron transfer (CET) system was integrated into small interfering RNA (siRNA) lipid nanoparticles (LNPs). The CET acceptor can be chemically excited using generated energy between donor and hydrogen peroxide, which triggers generation of reactive oxygen species (ROS), promoting membrane destabilization. Tetra-oleoyl tri-lysino succinoyl tetraethylene pentamine included as an ionizable lipopeptide with U-shaped topology effective siRNA encapsulation pH-induced escape. LNPs loaded components demonstrated more efficient escape, evidenced by galectin-8-mRuby reporter; ROS significantly augmented galectin-8 recruitment at least threefold compared control groups,

Language: Английский

Citations

0