Overcoming the non-kinetic activity of EGFR1 using multi-functionalized mesoporous silica nanocarrier for in vitro delivery of siRNA.

Autor: Parnian J; Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), P. O. Box 3353-5111, Tehran, Iran., Ma'mani L; Department of Nanotechnology, Agricultural Research Education and Extension Organization (AREEO), Agricultural Biotechnology Research Institute of Iran (ABRII), P. O. Box 31535-1897, Karaj, Iran., Bakhtiari MR; Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), P. O. Box 3353-5111, Tehran, Iran., Safavi M; Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), P. O. Box 3353-5111, Tehran, Iran. m.safavi@irost.ir.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Oct 14; Vol. 12 (1), pp. 17208. Date of Electronic Publication: 2022 Oct 14.
DOI: 10.1038/s41598-022-21601-w
Abstrakt: Triple-negative breast cancer (TNBC) does not respond to HER2-targeted and hormone-based medicines. Epidermal growth factor receptor 1 (EGFR1) is commonly overexpressed in up to 70% of TNBC cases, so targeting cancer cells via this receptor could emerge as a favored modality for TNBC therapy due to its target specificity. The development of mesoporous silica nanoparticles (MSNs) as carriers for siRNAs remains a rapidly growing area of research. For this purpose, a multi-functionalized KIT-6 containing the guanidinium ionic liquid (GuIL), PEI and PEGylated folic acid (FA-PEG) was designed. Accordingly, KIT-6 was fabricated and modified with FA-PEG and PEI polymers attached on the surface and the GuIL placed in the mesopores. Subsequent to confirming the structure of this multi-functionalized KIT-6- based nanocarrier using TEM, SEM, AFM, BET, BJH, DLS and Zeta Potential, it was investigated for uploading and transferring the anti-EGFR1 siRNAs to the MD-MBA-231 cell line. The rate of cellular uptake, cellular localization and endolysosomal escape was evaluated based on the fluorescent intensity of FAM-labelled siRNA using flowcytometry analysis and confocal laser scanning microscopy (CLSM). The 64% cellular uptake after 4 h incubation, clearly suggested the successful delivery of siRNA into the cells and, CLSM demonstrated that siRNA@[FA-PEGylated/PEI@GuIL@KIT-6] may escape endosomal entrapment after 6 h incubation. Using qPCR, quantitative evaluation of EGFR1 gene expression, a knockdown of 82% was found, which resulted in a functional change in the expression of EGFR1 targets. Co-treatment of chemotherapy drug "carboplatin" in combination with siRNA@[FA-PEGylated/PEI@GuIL@KIT-6] exhibited a remarkable cytotoxic effect in comparison to carboplatin alone.
(© 2022. The Author(s).)
Databáze: MEDLINE
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