Carboxymethyl dextran‐trimethyl chitosan coated superparamagnetic iron oxide nanoparticles: An effective siRNA delivery system for HIV‐1 Nef

Abstract

Gene therapy, including small interfering RNA (siRNA) technology, is one of the leading strategies that help to improve the outcomes of the current therapeutic systems against HIV-1 infection. The successful therapeutic application of siRNAs requires their safe and efficient delivery to specific cells. Here, we introduce a superparamagnetic iron oxide nanoparticle (SPION) for delivering siRNA against HIV-1 nef (anti-nef siRNA) into two cell lines, HEK293 and macrophage RAW 264.7.SPIONs were coated with trimethyl chitosan (TMC), and thereafter, different concentrations of SPION-TMC were coated with different ratios of a carboxymethyl dextran (CMD) to modify the physicochemical properties and improve the biological properties of the nanocarriers. The nanoparticles exhibited a spherical shape with an average size of 112 nm. The obtained results showed that the designed delivery route enhanced the uptake of siRNA into both HEK293 and RAW 264.7 cells compared with control groups. Moreover, CMD-TMC-SPIONs containing anti-nef siRNA significantly reduced the expression of HIV-1 nef in HEK293 stable cells. The modified siRNA-loaded SPIONs also displayed no toxicity or apoptosis-inducing

Modification of SPION nanocarriers for siRNA delivery: A therapeutic strategy against HIV infection

“…SPIONs were covered by two polymers (PEI and TMC) to obtain a stable and effective drug/ vaccine delivery nanocarrier system. In the literature, both polymers used here have indicated high potential for delivery of nucleic acids (DNA or RNA) into various cell types and have facilitated cell uptake by compacting nucleic acids into nanoparticles [7,15]. Furthermore, they are shown to protect nucleic acids from degradation caused by extracellular enzymes, and also could help nucleic acids escape from endolysosomes [10].…”

“…SPIONs were prepared through a co-precipitation approach [7]. In brief, 0.298 g of FeCl 2 .4H 2 O and 0.810 g of FeCl 3 .6H 2 O were dissolved in deionized water (in a nitrogen environment).…”

“…Therefore, SPIONs could be used as both diagnostic and therapeutic agents because of their unique characteristics [6]. Moreover, the mechanism of magnetic hyperthermia of SPIONs can be applied to suppress the HIV viral load, since hyperthermic temperatures increase the activity of cytotoxic T lymphocytes (CTLs), which can inhibit HIV replication [7]. On the contrary, due to the nonreproducibility of synthesis and agglomeration of the SPION colloidal suspensions, their clinical use have been limited [8,9].…”

“…To tackle these issues, the SPION surface can be coated with synthetic or natural polymers such as polyethylene glycol, alginate, dextran, chitosan and polyethylenimine. Therefore in our study, the surface of SPION was coated with trimethyl chitosan (TMC) and polyethylenimine (PEI) to prevent the agglomeration and to enhance the solubility of SPION [7]. These polymers could also promote the cell uptake through condensation of nucleic acids (DNA or RNA) into nanoparticles [3].…”

“…TMC is a derivative of chitosan (a biocompatible and non-toxic polymer) that displays a positive charge and great water solubility in a broad range of pH [10]. The positive charge of TMC can enhance the loading quantity of nucleic acids into nanoparticles [7]. Moreover, PEI is the most efficient polymer for nucleic acid delivery due to its high capacity of proton-buffering; although it is dose-dependent toxic [11,12].…”