Stealth magnetic nanocarriers of siRNA as platform for breast cancer theranostics

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Abstract

The endogenous mechanism of RNA interference is more and more used in research to obtain specific down-regulation of gene expression in diseases such as breast cancer. Currently, despite the new fields of study open up by RNA interference, the rapid degradation of siRNA by nucleases and their negative charges prevent them from crossing cell membranes. To overcome these limitations, superparamagnetic iron oxide nanoparticles (SPIONs) represent a promising alternative for nucleic acid delivery. Previously, we reported the magnetic siRNA nanovectors (MSN) formulation using electrostatic assembly of (1) SPIONs, also able to act as contrast agents for magnetic resonance imaging (MRI), (2) siRNA and (3) chitosan aiming at their protection and enhancing their transfection efficacy. However, these nanoparticles displayed low stability in biological suspensions and inefficient transfection of active siRNA.

This work aimed at upgrading MSN to Stealth MSN (S-MSN) by adding a polyethylene glycol coating to ensure colloidal stability and stealth properties. Furthermore, another polymer (poly-L-arginine) was added for efficient siRNA transfection and the quantitative composition of the formulation was adapted for biological purposes. Results showed that S-MSN provide high siRNA complexation and protection against enzymatic degradation. Green fluorescent protein (GFP) specific down-regulation on MDA-MB231/GFP cells was comparable to that of commercially available reagents, without observable cytotoxicity. According to our works, S-MSN appears as an effective formulation for in vitro siRNA specific delivery.

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