Development of anisamide-targeted PEGylated gold nanorods to deliver epirubicin for chemo-photothermal therapy in tumor-bearing mice

开发以茴香酰胺为靶点的聚乙二醇化金纳米棒,用于递送表柔比星,对肿瘤小鼠进行化学光热疗法

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作者:Limei Wang, Jin Pei, Zhongcheng Cong, Yifang Zou, Tianmeng Sun, Fionán Davitt, Adrià Garcia-Gil, Justin D Holmes, Caitriona M O'Driscoll, Kamil Rahme, Jianfeng Guo

Background

Gold nanorods (AuNRs), due to the optical and electronic properties namely the surface plasma resonance, have been developed to achieve the light-mediated photothermal therapy (PTT) for cancer. However, PTT alone may suffer from inefficient tumor killing. Recently, the combination of PTT and chemotherapy has been utilized to achieve synergistic anticancer effects.

Conclusion

These results demonstrate a promising strategy for clinical application of CPTT in cancer.

Methods

In this study, AuNRs capped with hexadecyltrimethylammonium bromide (CTAB), poly(acrylic acid) (PAA), and PEGylated anisamide (a ligand known to target the sigma receptor) have been developed to produce a range of negatively charged anisamide-targeted PEGylated AuNRs (namely Au-CTAB-PAA-PEG-AA) for the combination of PTT and chemotherapy (termed as chemo-photothermal therapy [CPTT]). Epirubicin (EPI, an anthracycline drug) was efficiently loaded onto the surface of Au800-CTAB-PAA-PEG-AA via the electrostatic interaction forming Au800-CTAB-PAA-PEG-AA.EPI complex.

Results

The resultant complex demonstrated pH-dependent drug release, facilitated nucleus trafficking of EPI, and induced antiproliferative effects in human prostate cancer PC-3 cells. When Au800-CTAB-PAA-PEG-AA.EPI complex was further stimulated with desired laser irradiation, the synergistic outcome was evident in PC-3 xenograft mice.

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