期刊
ACS NANO
卷 3, 期 10, 页码 3273-3286出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn900918w
关键词
mesoporous silica nanoparticles (MSNP); polyethyleneimine (PEI); transfection; plasmid DNA; siRNA; drug delivery
类别
资金
- NIAID NIH HHS [U19 AI070453] Funding Source: Medline
- NIEHS NIH HHS [R01ES015498, R01 ES016746, R01 ES015498] Funding Source: Medline
- Direct For Biological Sciences [0830117] Funding Source: National Science Foundation
- Div Of Biological Infrastructure [0830117] Funding Source: National Science Foundation
Surface-functionalized mesoporous silica nanoparticles (MSNP) can be used as an efficient and safe carrier for bioactive molecules. In order to make the MSNP a more efficient delivery system, we modified the surface of the particles by a functional group that enhances cellular uptake and allows nucleic acid delivery in addition to traditional drug delivery. Noncovalent attachment of polyethyleneimine (PEI) polymers to the surface not only increases MSNP cellular uptake but also generates a cationic surface to which DNA and siRNA constructs could be attached. While efficient for intracellular delivery of these nucleic acids, the 25 kD PEI polymer unfortunately changes the safety profile of the MSNP that is otherwise very safe. By experimenting with several different polymer molecular weights, it was possible to retain high cellular uptake and transfection efficiency while reducing or even eliminating cationic MSNP cytotoxicity. The particles coated with the 10 kD PEI polymer were particularly efficient for transducing HEPA-1 cells with a siRNA construct that was capable of knocking down GFP expression. Similarly, transfection of a GFP plasmid induced effective expression of the fluorescent protein in >70% cells in the population. These outcomes were quantitatively assessed by confocal microscopy and flow cytometry. We also demonstrated that the enhanced cellular uptake of the nontoxic cationic MSNP enhances the delivery of the hydrophobic anticancer drug, paclitaxel, to pancreatic cancer cells. In summary, we demonstrate that, by a careful selection of PEI size, it is possible to construct cationic MSNP that are capable of nucleotide and enhanced drug delivery with minimal or no cytotoxicity. This novel use of a cationic MSNP extends its therapeutic use potential.
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