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Enhancing WRAP-Based Nanoparticles for Small Interfering Ribonucleic Acid Delivery in pH-Sensitive Environments.
Giulia Di Gregorio1, Coélio Vallée2, Karidia Konate1
1PhyMedExp, University of Montpellier, INSERM, CNRS, 371 Av. Doyen Giraud, 34295, Montpellier, France.
Chemmedchem
|March 14, 2025
Summary
Researchers developed pH-sensitive nanoparticles using WRAP5 peptides and siRNA for targeted delivery in myocardial infarction. These nanoparticles effectively deliver therapeutic siRNA to injured heart cells, inhibiting apoptosis.
Area of Science:
- Biotechnology
- Nanomedicine
- Cardiovascular Research
Background:
- Small interfering RNAs (siRNA) are potent therapeutic agents but require effective delivery systems.
- Existing siRNA delivery systems include lipid- or peptide-based nanoparticles.
- Acute myocardial infarction involves ischemic heart tissue with a characteristic pH drop.
Purpose of the Study:
- To optimize WRAP5-based nanoparticles for pH-sensitive siRNA delivery in myocardial infarction.
- To investigate targeted delivery of siRNA to inhibit apoptosis in ischemic heart tissue.
- To evaluate the efficacy of PEGylated WRAP5 nanoparticles in a pH-dependent manner.
Main Methods:
- Conception and validation of WRAP5 peptide-forming nanoparticles with siRNA.
- Optimization of nanoparticles using pH-sensitive acyl hydrazone linkers to graft polyethylene glycol (PEG).
- Proof-of-concept study using siRNA to silence the Fas-associated death domain (FADD) protein in human vascular endothelial cells and hiPSC-derived cardiomyocytes at pH 5.
Main Results:
- PEGylated WRAP5 nanoparticles demonstrated pH-sensitive siRNA delivery.
- Specific FADD knockdown was achieved at pH 5 using optimized nanoparticles, unlike naked nanoparticles.
- The system showed targeted delivery and inhibition of apoptosis-related protein FADD.
Conclusions:
- Optimized WRAP5-based nanoparticles offer a novel therapeutic tool for myocardial infarction.
- pH-sensitive nanoparticle design facilitates targeted siRNA delivery to injured cells.
- This approach can inhibit reperfusion-induced apoptosis and enhance local therapeutic delivery.
Keywords:
acylhydrazonespH sensitivepeptide‐based nanoparticlessmall interfering ribonucleic acid deliverytargetingMore Related Videos
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