TY - JOUR TI - Protein kinase C inhibitor anchored BRD4 PROTAC PEGylated nanoliposomes for the treatment of vemurafenib-resistant melanoma AU - Fu, Yige AU - Rathod, Drishti AU - Patel, Ketan T2 - Experimental Cell Research AB - Limited treatment options and development of resistance to targeted therapy within few months pose significant challenges in the treatment of BRAF-mutated malignant melanoma. Moreover, extensive angiogenesis and vasculogenic mimicry promote the rapid progression of disease. The purpose of this study was to develop a protein kinase C inhibitor anchored BRD4 PROTAC (ARV) loaded PEGylated nanoliposomes (LARPC). Palmitoyl-dl-carnitine chloride (PC) was used as a protein kinase C inhibitor to provide a cationic surface charge to LARPC. The formulation was characterized for particle size, zeta potential, drug release and various cell culture assays using HUVEC and vemurafenib resistant melanoma cells. The particle size of LARPC was found to be 105.25 ± 2.76 nm with a zeta potential of +26.6 ± 6.25 mV. Inhibition of angiogenesis was demonstrated by ARV and LARPC using human umbilical vein endothelial cells (HUVEC)-based matrigel basement membrane model. Additionally, LARPC demonstrated very low IC50 with promising inhibition of vasculogenic mimicry channel formation, cell migration as well as colony formation in vemurafenib-resistant melanoma cell lines. Hence, the outcome of this combination therapy indicated the suitability of LARPC as a potential and novel approach for eradicating vemurafenib-resistant melanoma. DA - 2020/09/06/ PY - 2020 DO - 10.1016/j.yexcr.2020.112275 DP - ScienceDirect SP - 112275 J2 - Experimental Cell Research LA - en SN - 0014-4827 UR - http://www.sciencedirect.com/science/article/pii/S0014482720305243 Y2 - 2020/09/10/20:26:03 KW - ARV KW - PEGylated nanoliposomes KW - Palmitoyl--Carnitine chloride KW - Protein kinase C inhibitor KW - Vemurafenib-resistant melanoma ER -