Engineering and in vitro evaluation of acid labile cholesterol tethered MG132 nanoparticle fortargeting ubiquitin-proteasome system in cancer
| Title | Engineering and in vitro evaluation of acid labile cholesterol tethered MG132 nanoparticle fortargeting ubiquitin-proteasome system in cancer |
| Publication Type | Journal Article |
| Year of Publication | 2016 |
| Authors | Ghosh, C, Gupta, N, More, P, Sengupta, P, Mallick, A, Santra, MKumar, Basu, S |
| Journal | Chemistryselect |
| Volume | 1 |
| Issue | 16 |
| Pagination | 5099-5106 |
| Date Published | OCT |
| 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 beta-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. |
| DOI | 10.1002/slct.201601117 |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 0.00 |
Divison category:
Physical and Materials Chemistry