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Updated: Sep 15, 2025
Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Cleavable Cationic Carbosilane Dendrimers with pH-Tunable Charge as siRNA Carriers
Judith Recio-Ruiz1, Paulina Rycharska2,3, Małgorzata Grygiel2
1University of Alcala, Department of Organic and Inorganic Chemistry and Research Institute in Chemistry "Andrés M. Del Río" (IQAR), Madrid 28805, Spain.
Abstract:
Gene therapy is a cutting-edge technique for the prevention or treatment of diseases, which demands the development of biocompatible and efficient vectors. Additionally, for cancer therapy, a precise control on the vectors' response at different pH values is required due to the heterogeneity of the tumors' pH. Many nonviral vectors are based on quaternary ammonium compounds, thus exhibiting potential toxicity and persistence. In this work, we designed a new family of cationic carbosilane dendrimers, which exhibits two differential features: a pH-tunable charge, which can modulate the interaction between the nanocarrier and the siRNA, and a cleavable core, which can further enhance the release of the cargo. We thoroughly explored the structural and biophysical characteristics of the new dendrimers at different pH values: 4.5, 5.5, and 7.4. Additionally, biocompatibility in tumoral and nontumoral cells was evaluated along with the hemolytic effect. Finally, we provided a proof-of-concept for their use as pH-responsive nanocarriers of siRNA.
Insights
Researchers developed novel pH-responsive carbosilane dendrimers for gene therapy. These biocompatible nanocarriers offer tunable charge and cargo release, showing promise for targeted siRNA delivery in cancer treatment.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Gene Therapy
Background:
- Efficient and biocompatible vectors are crucial for gene therapy.
- Tumor microenvironments' varying pH necessitates pH-responsive nanocarriers for cancer therapy.
- Conventional nonviral vectors may exhibit toxicity and persistence issues.
Purpose of the Study:
- To design and characterize a new family of cationic carbosilane dendrimers.
- To evaluate the pH-tunable charge and cleavable core features for enhanced siRNA delivery.
- To assess the biocompatibility and potential of these dendrimers as pH-responsive nanocarriers.
Main Methods:
- Synthesis and structural characterization of carbosilane dendrimers.
- Exploration of biophysical properties at varying pH (4.5, 5.5, 7.4).
- In vitro evaluation of biocompatibility in tumoral and non-tumoral cells and hemolytic effect assessment.
Main Results:
- The novel carbosilane dendrimers demonstrated pH-tunable charge characteristics.
- A cleavable core was incorporated to facilitate cargo release.
- The dendrimers showed good biocompatibility and a proof-of-concept for pH-responsive siRNA delivery was established.
Conclusions:
- The designed carbosilane dendrimers represent a promising platform for pH-responsive gene delivery.
- Their tunable properties offer advantages for targeted cancer therapy.
- Further development could lead to safer and more effective gene therapy vectors.
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