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

Limei Wang,1,2 Jin Pei,1 Zhongcheng Cong,1 Yifang Zou,1 Tianmeng Sun,3 Fionán Davitt,4,5 Adrià Garcia-Gil,4,5 Justin D Holmes,4,5 Caitriona M O’Driscoll,6 Kamil Rahme,4,7 Jianfeng Guo1 1School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China; 2Department of Pharmacy, The General Hospital of FAW, Changchun 130011, China; 3The First Hospital of Jilin University, Changchun 130021, China; 4School of Chemistry and the Tyndall National Institute, University College Cork, Cork, Ireland; 5CRANN, Trinity College Dublin, Dublin, Ireland; 6Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland; 7Department of Sciences, Faculty of Natural and Applied Science, Notre Dame University (Louaize), Zouk Mosbeh 1200, Lebanon 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. 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. Conclusion: These results demonstrate a promising strategy for clinical application of CPTT in cancer. Keywords: gold nanoparticles, non-viral drug delivery, chemotherapy, photothermal therapy, synergistic effec