Targeted Nano-Drug Delivery of Colchicine against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles
by
Khaled AbouAitah 1,2,*
, 
Heba A. Hassan 3, Anna Swiderska-Sroda 1, Lamiaa Gohar 4, Olfat G. Shaker 5, Jacek Wojnarowicz 1, Agnieszka Opalinska 1, Julita Smalc-Koziorowska 6, Stanislaw Gierlotka 1 and Witold Lojkowski 1
Khaled AbouAitah 1,2,*, Heba A. Hassan 3, Anna Swiderska-Sroda 1, Lamiaa Gohar 4, Olfat G. Shaker 5, Jacek Wojnarowicz 1, Agnieszka Opalinska 1, Julita Smalc-Koziorowska 6, Stanislaw Gierlotka 1 and Witold Lojkowski 1
1
Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
2
Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza 12622, Egypt
3
Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza 12622, Egypt
4
Pharmacognosy Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Giza 12622, Egypt
5
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo 11511, Egypt
6
Laboratory of Semiconductor Characterization, Institute of High Pressure Physics, Polish Academy of Sciences, Sokolowska 29/37, 01-142 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(1), 144; https://doi.org/10.3390/cancers12010144
Received: 3 December 2019 / Revised: 25 December 2019 / Accepted: 3 January 2020 / Published: 7 January 2020
(This article belongs to the Special Issue Role of Natural Bioactive Compounds in the Rise and Fall of Cancers)
Antimitotics are important anticancer agents and include the natural alkaloid prodrug colchicine (COL). However, a major challenge of using COL as an anticancer drug is its cytotoxicity. We developed a novel drug delivery system (DDS) for COL using mesoporous silica nanoparticles (MSNs). The MSNs were functionalized with phosphonate groups, loaded with COL, and coated with folic acid chitosan-glycine complex. The resulting nanoformulation, called MSNsPCOL/CG-FA, was tested for action against cancer and normal cell lines. The anticancer effect was highly enhanced for MSNsPCOL/CG-FA compared to COL. In the case of HCT116 cells, 100% inhibition was achieved. The efficiency of MSNsPCOL/CG-FA ranked in this order: HCT116 (colon cancer) > HepG2 (liver cancer) > PC3 (prostate cancer). MSNsPCOL/CG-FA exhibited low cytotoxicity (4%) compared to COL (~60%) in BJ1 normal cells. The mechanism of action was studied in detail for HCT116 cells and found to be primarily intrinsic apoptosis caused by an enhanced antimitotic effect. Furthermore, a contribution of genetic regulation (metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1), and microRNA (mir-205)) and immunotherapy effects (angiopoietin-2 (Ang-2 protein) and programmed cell death protein 1 (PD-1) was found. Therefore, this study shows enhanced anticancer effects and reduced cytotoxicity of COL with targeted delivery compared to free COL and is a novel method of developing cancer immunotherapy using a low-cost small-molecule natural prodrug.
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Keywords:
colchicine alkaloid; colon cancer cells; mesoporous silica nanoparticles; targeted delivery system; apoptosis; PD-1 immune checkpoint inhibitor and cancer immunotherapy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
AbouAitah, K.; Hassan, H.A.; Swiderska-Sroda, A.; Gohar, L.; Shaker, O.G.; Wojnarowicz, J.; Opalinska, A.; Smalc-Koziorowska, J.; Gierlotka, S.; Lojkowski, W. Targeted Nano-Drug Delivery of Colchicine against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles. Cancers 2020, 12, 144.
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