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Enhanced Gene Delivery and Expression using Intraosseous Injection of Chitosan Nanoparticles Encapsulated Adenine Base Editor Plasmids
Published on: May 16, 2025
Nanosized bioceramic particles could function as efficient gene delivery vehicles with target specificity for the
11School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
Gene Therapy
|March 9, 2007
Summary
Silica nanoparticles coated with protamine sulfate effectively deliver genes in vivo, enhancing immune responses and reducing tumors. This offers a promising non-viral vector for gene therapy applications.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Gene Therapy
Background:
- Non-viral vectors are crucial for safe gene delivery.
- Bioceramic nanoparticles offer potential as gene delivery vectors.
- Optimizing nanoparticle properties is key for efficient gene transfection.
Purpose of the Study:
- To evaluate silica (SiO(2)), hydroxyapatite (HA), and zirconia (ZrO(2)) nanoparticles as non-viral gene delivery vectors.
- To assess the efficacy of protamine sulfate (PS)-coated nanoparticles for in vitro and in vivo gene delivery.
- To investigate the immunomodulatory and anti-tumor effects of nanoparticle-mediated gene delivery.
Main Methods:
- Synthesis and characterization of nanosized bioceramic particles (SiO(2), HA, ZrO(2)).
- Complexation of plasmid DNA with PS-coated nanoparticles (nanoplexes).
- In vitro transfection assays in cell lines, including assessment in 50% serum.
- In vivo gene delivery studies in mice via intraperitoneal injection, monitoring transgene expression and immune responses.
Main Results:
- PS-coated SiO(2) and HA nanoparticles efficiently complexed with plasmid DNA, enhancing in vitro transgene expression.
- PS-SiO(2)-DNA nanoplexes showed superior transfection efficiency compared to ZrO(2) and were effective in 50% serum.
- In vivo studies demonstrated high splenic transgene expression with PS-SiO(2)-luciferase DNA nanoplexes lasting over 48 hours.
- PS-SiO(2)-pNGVL-hFLex-MUC-1 nanoplexes induced Flt-3L, IL-2, and interferon-gamma production, mounting anti-tumor immune responses and causing tumor regression.
Conclusions:
- Negatively charged silica nanoparticles coated with protamine sulfate are effective non-viral vectors for in vivo gene delivery.
- This approach elicits significant transgene expression and potent anti-tumor immune responses, leading to tumor regression.
- PS-SiO(2) nanoparticles represent a promising platform for therapeutic gene delivery and cancer immunotherapy.
