01789nas a2200205   4500008004100000245014600041210006900187260000800256300001400264490000600278520103400284100002401318700001601342700001701358700002201375700001901397700002501416700001801441856012401459       2016                        eng d00aEngineering and in vitro evaluation of acid labile cholesterol tethered MG132 nanoparticle fortargeting ubiquitin-proteasome system in cancer0 aEngineering and in vitro evaluation of acid labile cholesterol t  cOCT  a5099-51060 v13 aIn 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.1 aGhosh, Chandramouli1 aGupta, Neha1 aMore, Piyush1 aSengupta, Poulomi1 aMallick, Abhik1 aSantra, Manas, Kumar1 aBasu, Sudipta  uhttps://library.ncl.res.in/content/engineering-and-vitro-evaluation-acid-labile-cholesterol-tethered-mg132-nanoparticle