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

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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.

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Abbreviations

APTES:

3-aminopropyltriethoxysilane

CQ:

chloroquine

CTAB:

N-cetyltrimethylammonium bromide

DMEM:

Dulbecco’s modified Eagle’s medium

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

MPA:

3-mercaptopropionic acid

MPTMS:

3-mercaptopropyltrimethoxysilane

MSN:

mesoporous silica nanoparticles

PDEAEMA:

poly(2-(diethylamino)ethylmethacrylate)

PEG:

poly(ethylene glycol)

PEI:

polyethyleneimine

PDMAEMA:

poly(2-(dimethylamino)ethylmethacrylate)

PMSN:

PEG-coated MSN

TEOS:

tetraethylorthosilicate

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ACKNOWLEDGMENTS

This work was supported by NIH Grant EB0043588 from the National Institute of Biomedical Imaging and Bioengineering.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan, 48202, USA

    Shanta Raj Bhattarai, Amit Wani & David Oupicky

  2. Department of Chemistry, Wayne State University, Detroit, Michigan, 48202, USA

    Elayaraja Muthuswamy, Michal Brichacek, Antonio L. Castañeda & Stephanie L. Brock

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  1. Shanta Raj Bhattarai
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  2. Elayaraja Muthuswamy
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  3. Amit Wani
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  4. Michal Brichacek
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  7. David Oupicky
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Correspondence to David Oupicky.

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Bhattarai, S.R., Muthuswamy, E., Wani, A. et al. Enhanced Gene and siRNA Delivery by Polycation-Modified Mesoporous Silica Nanoparticles Loaded with Chloroquine. Pharm Res 27, 2556–2568 (2010). https://doi.org/10.1007/s11095-010-0245-0

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