Targeted Nano-Drug Delivery of Colchicine Against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 Jan 16

PMID 31936103

Citations 28

Authors

Khaled AbouAitah

Heba A Hassan

Anna Swiderska-Sroda

Lamiaa Gohar

Olfat G Shaker

Jacek Wojnarowicz

Agnieszka Opalinska

Julita Smalc-Koziorowska

Stanislaw Gierlotka

Witold Lojkowski

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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