Recent Advances in Asialoglycoprotein Receptor and Glycyrrhetinic Acid Receptor-Mediated and/or pH Responsive Hepatocellular Carcinoma-Targeted Drug Delivery.
Curr Med Chem. 2020 May 04;:
Authors: Li YL, Zhu XM, Liang H, Orvig C, Chen ZF
BACKGROUND: Hepatocellular carcinoma (HCC) seriously affects human health, especially, it easily develop multi-drug resistance (MDR) result in treatment failure. There is an urgent need to develop highly effective and low-toxicity therapeutic agents to treat HCC and overcome its MDR. Targeted drug delivery systems (DDS) for cancer therapy, including nanoparticles, lipids, micelles and liposomes, have been studied for decades. Recently, more and more attentions have been paid to multifunctional DDS containing various ligands such as polymer moieties, targeting moieties, and acid-labile linkages. The polymer moieties such as poly(ethylene glycol) (PEG), chitosan, hyaluronic acid, pullulan, poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO) protect DDS from degradation. Asialoglycoprotein receptor (ASGPR) and glycyrrhetinic acid receptor (GAR) are the most often used as the targeting moieties, which are overexpressed on hepatocytes. Acid-labile linkage, catering for the pH difference between tumor cells and normal tissue, has been utilized to release drugs at tumor tissue.
OBJECTIVES: This review provides a summary on the recent progresses in ASGPR and GAR-mediated and/or pH responsive HCC-targeted drug delivery.
CONCLUSION: The multifunctional DDS may prolong systemic circulation, continuously release drugs, increase drugs tumor accumulation at targeted site,enhance anticancer effect, and reduce side effects both in vitro or vivo. But it is rarely used to investigate MDR of HCC, it is need to further study before in clinical.
PMID: 32368967 [PubMed - as supplied by publisher]