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Poly-L-Lysine Doped FmocFF Nanogels as Delivery Platforms for siRNA
Elisabetta Rosa1, Luigi Romano1, Virgilio Piccolo1
1Department of Pharmacy and Interuniversity Research Centre on Bioactive Peptides (CIRPeB) "Carlo Pedone", University of Naples "Federico II", Via T. De Amicis 95, Naples 80145, Italy.
ACS Applied Bio Materials
|May 13, 2026
Summary
Cationic nanogels (NGs) effectively encapsulate and release short interfering RNA (siRNA) for cellular delivery. These peptide-based nanogels show promise as safe nanoplatforms for gene silencing applications.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Gene Delivery
Background:
- Developing effective delivery systems for short interfering RNA (siRNA) is crucial for gene therapy.
- Cationic nanogels (NGs) offer potential as carriers due to their tunable properties.
Purpose of the Study:
- To formulate and characterize cationic nanogels (NGs) for efficient siRNA delivery.
- To evaluate the loading, release, and cellular uptake of siRNA-loaded NGs.
Main Methods:
- Mixed hydrogels of Fmoc-FF peptide and poly-l-Lysine (PLL) were prepared using a solvent-switch method.
- Injectable NGs were generated via sub-micronization and loaded with siRNA-Cy3.
- siRNA encapsulation, release kinetics, and cellular internalization were assessed.
Main Results:
- NGs with a hydrodynamic diameter of 284 nm and a zeta potential of +31 mV were produced.
- Efficient siRNA-Cy3 encapsulation (98%) and sustained release (70% in 72 h) were achieved.
- Preliminary in vitro studies confirmed NG internalization by HEK293 cells via endocytosis with a good safety profile.
Conclusions:
- Cationic polypeptide-based NGs are effective nanoplatforms for siRNA delivery.
- The developed NG formulation demonstrates potential for therapeutic gene silencing applications.
