Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA. Electronic address:
Published: August 2021
AI Article Synopsis
Article Abstract
Multidrug resistance-associated protein 7 (MRP7) is an important member of ABC transporter superfamily and has been revealed to mediate the cross-membrane translocation of a wide range of chemotherapeutic agents including taxanes, epothilones, Vinca alkaloids, Anthracyclines and Epipodophyllotoxins.In our previous study, a 1,2,3-triazole-pyrimidine hybridCMP25was synthesized and found able to efficiently reverse multidrug resistance (MDR) mediated by P-glycoprotein. In this study, we evaluated the efficacy of compound CMP25in reversing MDR mediated by MRP7in vitro. The results showed that CMP25significantly sensitized MRP7-overexpressing cells to anticancer drugs that are MRP7 substrates. Mechanistic study showed that CMP25reversed MRP7-mediated MDR by increasing the intracellular accumulation of anticancer drugs and decreasing drug efflux, without altering protein expression level or subcellular localization. Currently, very few studies on synthetic MRP7 modulators have been published. Our findings provide a valuable prototype for designing drugs to combine with conventional anticancer drugs to overcome MDR-mediated by MRP7.
Cellular mechanical dysregulation can lead to diseases and conditions like tumorigenesis. Drug delivery systems that recognize and respond to specific cellular mechanical characteristics are potentially useful for targeted therapy. We report here the creation of a DNA mechanical nanovehicle that is responsive to cell surface receptor-mediated tensile forces, which can then correspondingly deliver an anticancer drug in situ.
Platinum (Pt)-based anticancer agents exhibit a lack of selectivity in the treatment of osteosarcoma, resulting in significant toxicity. Furthermore, immune surveillance withinthe tumor microenvironment impedes the uptake of platinum drugs by osteosarcoma cells. To overcome these challenges, an oxaliplatin-based Pt prodrug amphiphile (Lipo-OXA-ALN) was designed and synthesized by incorporatingan osteosarcoma-targeting alendronate (ALN) alongside a lipid tail.
Vascular endothelial growth factor receptor-3 (VEGFR-3) plays an indispensable role in lymphangiogenesis. Previous findings suggest that blocking the VEGFR-3 signaling pathway can inhibit lymph node metastasis effectively, thus reducing the incidence of distant metastasis. The development of new VEGFR-3-targeting drugs for early detection and effective treatments is, therefore, urgently required.
This study presents an innovative approach to improve implant biointegration and reduce implant-associated infections using porous poly(vinyl formal) nanocomposite matrices incorporated with gold nanoparticles and antimicrobial/anticancer drugs for plastic surgery applications. The porous matrices were characterized using physicochemical techniques and in vitro biochemical assays. The results demonstrated the biocompatibility of PVF nanocomposites and their potential for functionalization with various bioactive molecules and drugs, thereby enhancing their therapeutic efficacy.
Selective inhibition of histone deacetylase 8 (HDAC8) has emerged as a promising approach for treating various diseases, including cancer. However, finding key structural features for HDAC8 inhibition and developing effective and selective HDAC8 inhibitors (HDAC8s) pose significant challenges. In the past few years, the development of various scaffolds for inhibiting HDAC8 has significantly risen and the quest continues.
