TAT-Modified Gold Nanoparticle Carrier with Enhanced Anticancer Activity and Size Effect on Overcoming Multidrug Resistance

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 IC 50 value of ANS-TAT-AuNPs 3.8 nm reduced by 11.28- (24 h) and 12.64-fold (48 h) after incubation with liver hepatocellular carcinoma HepG 2 cells 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-AuNPs 22.1 nm decreased dramatically to 1.48 (24 h) and 2.20 (48 h), while that of ANS-TAT-AuNPs 3.8 nm decreased to 7.64 (24 h) and 7.77 (48 h), indicating that ANS-TAT-AuNPs 22.1 nm could 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).