# Cleavable Cationic Carbosilane Dendrimers with pH-Tunable Charge as siRNA Carriers

## 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.

## Key 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 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.