Enhanced Gene and siRNA Delivery by Polycation-Modified Mesoporous Silica Nanoparticles Loaded with Chloroquine

Abstract

Purpose To prepare mesoporous silica-based delivery systems capable of simultaneous delivery of drugs and nucleic acids. Methods The surface of mesoporous silica nanoparticles (MSN) was modified with poly(ethylene glycol) (PEG) and poly(2-(dimethylamino)ethylmethacrylate) (PDMAEMA) or poly (2-(diethylamino)ethylmethacrylate) (PDEAEMA). The particles were then loaded with a lysosomotropic agent chloroquine (CQ) and complexed with plasmid DNA or siRNA. The ability of the synthesized particles to deliver combinations of CQ and nucleic acids was evaluated using luciferase plasmid DNA and siRNA targeting luciferase and GAPDH. Results The results show a slow partial MSN dissolution to form hollow silica nanoparticles in aqueous solution. The biological studies show that polycation-modified MSN are able to simultaneously deliver CQ with DNA and siRNA. The co-delivery of CQ and the nucleic acids leads to a significantly increased transfection and silencing activity of the complexes compared with MSN not loaded with CQ. Conclusion PEGylated MSN modified with polycations are promising delivery vectors for combination drug/nucleic acid therapies.

Functionalized large pore mesoporous silica nanoparticles for gene delivery featuring controlled release and co-delivery

“…It is very soluble in water with the solubility up to 1 mg/ml. 14,33 However, the nature of PDMAEA-LPMSN that can PDMAEA-LPMSN were similar, around 1200 µg/ml, which can be explained by the very low toxicity of PDMAEA 23,24 and unmodified LPMSN. 15 Similar to PDMAEA-LPMSN, Chl-PDMAEA-LPMSN did not affect the cell viability.…”

Recent applications of the combination of mesoporous silica nanoparticles with nucleic acids: development of bioresponsive devices, carriers and sensors

“…This produced a disassembly of the cationic surface that allowed the effective release of the therapeutic nucleotide. In the first model, by Bhattarai et al, after validation with the anti-luciferase siRNA, the authors employed the glyceraldehyde 3-phosphate dehydrogenase (GADPH) siRNA able to arrest glycolysis, which in combination with CLQ reduced significantly the cell viability 162 (Entry 6, Table 2). In the later example, the authors improved the grafting step of polymer through a click-process.…”

15 years on siRNA delivery: Beyond the State-of-the-Art on inorganic nanoparticles for RNAi therapeutics

“…However, more polymers have been used for conjugation, e.g. poly-arginine [105], derivatives of polymaleic acid [70] and ethylmethacrylate [106]. Besides, Pierre et al used a combined functionalization of MNPs with two kinds of polymers, being able to modulate the net charge more effectively [107].…”