Cleavable Cationic Carbosilane Dendrimers with pH-Tunable Charge as siRNA Carriers
Judith Recio-Ruiz, Paulina Rycharska, Małgorzata Grygiel, Sylwia Michlewska, Maria Bryszewska, Maksim Ionov, Francisco Javier de la Mata, Sandra García-Gallego
TL;DR
This paper introduces new pH-sensitive nanocarriers for delivering siRNA, which could improve gene therapy by responding to different tumor pH levels.
Contribution
A new family of cleavable cationic carbosilane dendrimers with pH-tunable charge is designed for siRNA delivery.
Findings
The dendrimers show pH-tunable charge, affecting their interaction with siRNA.
They demonstrated biocompatibility in both tumoral and nontumoral cells.
The nanocarriers showed potential as pH-responsive siRNA delivery systems.
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…
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Taxonomy
TopicsRNA Interference and Gene Delivery · Dendrimers and Hyperbranched Polymers · Advanced biosensing and bioanalysis techniques