Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs
Open accessAbstract
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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Certain coatings, such as polyethylenimine, have been claimed to show activation of immunological pathways in vitro, as exemplified by M1-like activation of macrophages induced by PEI-coated SPION.
“Certain coatings, such as polyethylenimine (PEI), have been claimed to show an activation of immunological pathways in vitro, as exemplified e.g. an M1-like activation of macrophages induced by PEI-coated SPION [123, 124].”
From Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications (2019) · cites this paper as [123]
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- Authors
- Xia, T., Kovochich, M., Liong, M., Meng, H., Kabehie, S., George, S., Zink, J. I., & Nel, A. E.
- Affiliations
- University of California, Los Angeles (US)
- Division of NanoMedicine, Department of Medicine
- Department of Chemistry & Biochemistry
- California NanoSystems Institute (US)
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-09-09
- Volume
- 3
- Issue
- 10
- Pages
- 3273-3286
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC3900639
- OpenAlex
- W1983361018
- Cited by
- 933
- References
- 50
- Citations by year
- 2026: 29 · 2025: 34 · 2024: 26 · 2023: 40 · 2022: 52 · 2021: 52 · 2020: 60 · 2019: 62 · 2018: 50 · 2017: 72 · 2016: 73 · 2015: 65 · 2014: 83 · 2013: 78 · 2012: 76
- FWCI
- 20.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u19ai070453-05)
- National Institute of Allergy and Infectious Diseases (U19 AI-070453)
- National Institute of Environmental Health Sciences (R01ES015498, R01ES016746)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Materials Chemistry › Mesoporous Materials and Catalysis
- Keywords
- mesoporous silica nanoparticles, polyethyleneimine coating, cellular uptake, siRNA delivery, DNA transfection, cationic nanoparticles, cytotoxicity, polymer molecular weight, paclitaxel delivery, pancreatic cancer cells, nanoparticle drug delivery
- MeSH terms
- Animals, Biological Transport, DNA, Drug Carriers, Humans, Plasmids, Polyethyleneimine, Silicon Dioxide, Porosity, Paclitaxel, RNA, Small Interfering, Cell Line, Tumor, Nanomedicine, Mice, Nanoparticles, Chemical Phenomena
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