Enhanced gene and siRNA delivery by polycation-modified mesoporous silica nanoparticles loaded with chloroquine.
OBJECTIVE
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.


CONCLUSIONS
PEGylated MSN modified with polycations are promising delivery vectors for combination drug/nucleic acid therapies.
Bhattarai
Shanta Raj
SR
Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan 48202, USA.
Muthuswamy
Elayaraja
E
Wani
Amit
A
Brichacek
Michal
M
Castañeda
Antonio L
AL
Brock
Stephanie L
SL
Oupicky
David
D
D002412:Cations; D002738:Chloroquine / Q000737:chemistry*; D004247:DNA / Q000235:genetics; D018014:Gene Transfer Techniques; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D012822:Silicon Dioxide; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
D002412:Cations; D034741:RNA, Small Interfering; D012822:Silicon Dioxide; D002738:Chloroquine; D004247:DNA