Targeted delivery of Elesclomol to colorectal cancer using a drug delivery system based on magnetic mesoporous silica nanoparticles

Subject Areas : شیمی آلی

Mojtaba Tarin ¹ , Maryam Babaei ² , Hossein Eshghi ³ , Maryam Matin ⁴ , Amir Shokooh Saljooghi ⁵

1 - PhD Student of Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
2 - PhD of Organic Chemistry, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
3 - Professor of Organic Chemistry, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
4 - Professor of Biology, Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
5 - Associate Prof. of Inorganic Chemistry, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

Received: 2023-05-15 Accepted : 2023-07-04 Published : 2023-11-22

Keywords: Colorectal cancer, Controlled release, Targeted Therapy, Mesoporous silica nanoparticles, Elesclomol,

Abstract :

In this research, the targeted delivery of elesclomol to colorectal cancer cells was explored through the development of magnetic mesoporous silica nanoparticles (MMSNs) loaded with elesclomol and surface modification with gold gatekeepers, bifunctional polyethylene glycol (PEG) polymer, and epithelial cell adhesion molecule (EpCAM) aptamers to improve drug delivery performance. The physicochemical properties of nanocarriers were characterized and the cellular toxicity of elesclomol, and nano-delivery system with and without EpCAM aptamer modification has been investigated in vitro. High resolution transmission electron microscopy (HRTEM) and field emission scanning electron microscopy (FESEM) showed that MMSNs had a uniform spherical morphology with a diameter of 19 nm and a negative surface charge. Elesclomol was successfully encapsulated in the open porous structure of the nanocarrier. The encapsulation efficiency (EE) and drug loading capacity (LC) were about 88% and 39%, respectively. Moreover, the prepared Au-ELC-MMSN-NH2 displayed pH responsive and sustained drug release within 96 h. Targeted nano-delivery systems were prepared with a final diameter of 89 nm and a negative surface charge. The MTT assay revealed that the targeted nano-delivery system induced highly effective cytotoxicity on colorectal cancer cells-expressing EpCAM aptamer (HT-29) compared to the CHO cells. This engineered nano-platform is a promising elesclomol replacement therapy for colorectal cancer. However, further experiments are required before it can be practiced in the clinic.

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