title: A Redox-Sensitive and RAGE-Targeting Nanocarrier for Hepatocellular Carcinoma Therapy.
abstract: Hepatocellular carcinoma (HCC) is an aggressive malignancy and the second leading cause of cancer death worldwide. Most current therapeutic agents lack the tumor-targeting efficiency and result in a nonselective biodistribution in the body. In our previous study, we identified a peptide Ala-Pro-Asp-Thr-Lys-Thr-Gln (APDTKTQ) that can selectively bind to the receptor of advanced glycation end-products (RAGE), an immunoglobulin superfamily cell surface molecule overexpressed during HCC malignant progression. Here, we report the design of a mixed micelles system modified with this peptide to target HCC cells. Specifically, we modified Pluronic F68 (F68) with APDTKTQ (F68-APDTKTQ), and we conjugated d-α-tocopheryl polyethylene glycol succinate (TPGS) with poly(lactic-co-glycolic acid) (PLGA) by a disulfide linker (TPGS-S-S-PLGA). We mixed TPGS-S-S-PLGA and F68-APDTKTQ (TSP/FP) to form a micelle, followed by the loading of oridonin (ORI). The prepared micelles showed a homogeneously spherical shape without aggregation, triggered an increased cellular uptake, and induced apoptosis in more cells than did the free ORI. Taken together, these results demonstrate the potential of this APDTKTQ-modified ORI-loaded TSP/FP mixed micelle system as a promising strategy for HCC-targeting therapy.
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau 999078, China.
authors: Xiao-Bin
authors: XB
authors: Fang
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau 999078, China.
authors: Ying-Qi
authors: YQ
authors: Xu
authors: Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States.
authors: Hon-Fai
authors: HF
authors: Chan
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau 999078, China.
authors: Chun-Ming
authors: CM
authors: Wang
authors: Qing
authors: Q
authors: Zheng
authors: Fei
authors: F
authors: Xiao
authors: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Macau 999078, China.
authors: Mei-Wan
authors: MW
authors: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008113:Liver Neoplasms / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D010084:Oxidation-Reduction / Q000187:drug effects; D010455:Peptides / Q000737:chemistry; D020442:Poloxamer; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D045786:Diterpenes, Kaurane; D017127:Glycation End Products, Advanced; D008823:Micelles; D010455:Peptides; C011959:oridonin; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols
keywords: HCC; RAGE; oridonin; pluronic F68; redox-sensitivity