Ghosh , C. and Gupta , N. and More , P. and GhoshSengupta , P. and Mallick , A. and Santra , M.K and Basu, S. (2016) Engineering and In Vitro Evaluation of Acid Labile Cholesterol Tethered MG132 Nanoparticle for Targeting Ubiquitin‐Proteasome System in Cancer. Chemistry Select., 1 (16). 5099-5106 .

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Abstract

In recent years, proteasome has evolved as one of the important alternative targets in cancer chemotherapy. However, selective targeting of proteasome system in cancer cells still remains a major challenge. To address this, a potent peptide based proteasome inhibitor MG132 was chemically conjugated with biocompatible-biodegradable cholesterol by acid cleavable hydrazone linkage. Spherical nanoparticles (MG132-NPs) were engineered from cholesterol-MG132 conjugate. Increased amount of free MG132 was released from these nanoparticles in acidic environment compared to physiological milieu in a slow and controlled manner. These MG132-NPs were taken up by breast cancer MCF7 cells into lysosomes within 6 h. Proteasome system was inhibited by these MG132-NPs leading to stabilization of β-catenin, cyclin A and cyclin B in HEK-293T cells. Interestingly, MG132-NPs induced much improved cell death in drug resistant MDA-MB-231 cells with insignificant toxicity in healthy cells (HEK293 and L929) even in higher concentration.

Item Type:	Article
Subjects:	Cancer Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	29 Nov 2017 06:33
Last Modified:	29 Nov 2017 06:33
URI:	http://nccs.sciencecentral.in/id/eprint/468

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