title: TAT-Modified Gold Nanoparticle Carrier with Enhanced Anticancer Activity and Size Effect on Overcoming Multidrug Resistance.
abstract: Highly efficient targeted delivery is crucial for successful anticancer chemotherapy. In this study, we developed a drug delivery system ANS-TAT-AuNP that loads anticancer molecule 2-(9-anthracenylmethylene)-hydrazinecarbothioamide (ANS) via conjugation with cell-penetrating peptide TAT modified AuNPs. The in vitro study showed that the IC50value of ANS-TAT-AuNPs3.8 nmreduced by 11.28- (24 h) and 12.64-fold (48 h) after incubation with liver hepatocellular carcinoma HepG2cells compared to that of free ANS, suggesting that TAT modified AuNPs could enhance the antiproliferative activity of ANS. Also, ANS-TAT-AuNPs showed a size effect on overcoming multidrug resistance (MDR). The potential of ANS-TAT-AuNPs in overcoming MDR was assessed with MCF-7/ADR drug-resistant cell line, the drug resistance index (DRI) of which was extremely high (>190). The DRI of ANS-TAT-AuNPs22.1 nmdecreased dramatically to 1.48 (24 h) and 2.20 (48 h), while that of ANS-TAT-AuNPs3.8 nmdecreased to 7.64 (24 h) and 7.77 (48 h), indicating that ANS-TAT-AuNPs22.1 nmcould treat extremely resistant MCF-7/ADR cancer cells as drug sensitive ones. The data suggest that the larger AuNPs had more profound effect on overcoming MDR, which could effectively prevent drug efflux due to their size being much larger than that of the p-glycoprotein channel (9-25 Å).
authors.forename: Rui-Hui
authors.initials: RH
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
authors.forename: Jun
authors.initials: J
authors.lastname: Deng
authors.forename: Chen-Jie
authors.identifier: http://orcid.org/0000-0003-1450-1271
authors.initials: CJ
authors.lastname: Fang
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health , Bethesda, Maryland 20892, United States.
authors.forename: Xiaoyuan
authors.identifier: http://orcid.org/0000-0002-9622-0870
authors.initials: X
authors.lastname: Chen
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006046:Gold; D006801:Humans; D061986:MCF-7 Cells; D053768:Metal Nanoparticles
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006046:Gold; D004317:Doxorubicin
keywords: AuNPs; TAT; anthracene derivatives; antiproliferation; size effect on MDR