The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Engineered Design of Mesoporous Silica Nanoparticles to Deliver Doxorubicin and P-Glycoprotein siRNA to Overcome Drug Resistance in a Cancer Cell Line
Open accessAbstract
Overexpression of drug efflux transporters such as P-glycoprotein (Pgp) protein is one of the major mechanisms for multiple drug resistance (MDR) in cancer cells. A new approach to overcome MDR is to use a co-delivery strategy that utilizes a siRNA to silence the expression of efflux transporter together with an appropriate anticancer drug for drug resistant cells. In this paper, we report that mesoporous silica nanoparticles (MSNP) can be functionalized to effectively deliver a chemotherapeutic agent doxorubicin (Dox) as well as Pgp siRNA to a drug-resistant cancer cell line (KB-V1 cells) to accomplish cell killing in an additive or synergistic fashion. The functionalization of the particle surface with a phosphonate group allows electrostatic binding of Dox to the porous interior, from where the drug could be released by acidification of the medium under abiotic and biotic conditions. In addition, phosphonate modification also allows exterior coating with the cationic polymer, polyethylenimine, which endows the MSNP to contemporaneously deliver Pgp siRNA. The dual delivery of Dox and siRNA in KB-V1 cells was capable of increasing the intracellular as well as intranuclear drug concentration to levels exceeding that of free Dox or the drug being delivered by MSNP in the absence of siRNA codelivery. These results demonstrate that it is possible to use the MSNP platform to effectively deliver a siRNA that knocks down gene expression of a drug exporter that can be used to improve drug sensitivity to a chemotherapeutic agent.
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Cites
Cancer nanotechnology: opportunities and challenges
Ferrari, M. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1566 · Cited by 4,558
Targeting multidrug resistance in cancer
Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1984 · Cited by 3,609
Xia, T., Kovochich, M., Liong, M., Meng, H., Kabehie, S., George, S., Zink, J. I., & Nel, A. E. (2009) · ACS Nano · doi:10.1021/nn900918w · Cited by 933
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Cited by
Mesoporous silica nanoparticles in biomedical applications
Li, Z., Barnes, J. C., Bosoy, A., Stoddart, J. F., & Zink, J. I. (2012) · Chemical Society Reviews · doi:10.1039/c1cs15246g · Cited by 1,907
Self-citationThe current state and future directions of RNAi-based therapeutics
Setten, R. L., Rossi, J. J., & Han, S.-P. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0017-4 · Cited by 1,443
He, C., Lu, K., Liu, D., & Lin, W. (2014) · Journal of the American Chemical Society · doi:10.1021/ja4098862 · Cited by 885
Wang, F., Wang, Y.-C., Dou, S., Xiong, M.-H., Sun, T.-M., & Wang, J. (2011) · ACS Nano · doi:10.1021/nn200007z · Cited by 813
Physicochemical Properties Determine Nanomaterial Cellular Uptake, Transport, and Fate
Zhu, M., Nie, G., Meng, H., Xia, T., Nel, A., & Zhao, Y. (2013) · Accounts of Chemical Research · doi:10.1021/ar300031y · Cited by 803
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Metadata
- Authors
- Meng, H., Liong, M., Xia, T., Li, Z., Ji, Z., Zink, J. I., & Nel, A. E.
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-07-14
- Volume
- 4
- Issue
- 8
- Pages
- 4539-4550
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- OpenAlex
- W2057256078
- Cited by
- 902
- References
- 3
- FWCI
- 27.47
- Type
- journal article
- Language
- en
- Open access
- green
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