Background: The existing chemo/radiotherapy fail to eliminate cancer cells due to the restriction of either drug resistance or radio tolerance. The predicament urges researchers to continuously explore alternative strategy for achieving a potent curative effect. 
Methods: Functional chlorin gold nanorods (Ce6-AuNR@SiO₂-d-CPP) were fabricated aiming at treating breast cancer by photothermal/photodynamic therapy (PTT/PDT). The nanostructure was developed by synthesizing Au nanorods as the photothermal conversion material, and by coating the pegylated mesoporous SiO₂ as the shell for entrapping photosensitizer Ce6 and for linking the D-type cell penetrating peptide (d-CPP). The function of Ce6-AuNR@SiO₂-d-CPP was verified on human breast cancer MCF-7 cells and MCF-7 cells xenografts in nude mice. 
Results: Under combinational treatment of PTT and PDT, Ce6-AuNR@SiO₂-d-CPP demonstrated a strong cytotoxicity and apoptosis inducing effects in breast cancer cells in vitro, and a robust treatment efficacy in breast cancer-bearing nude mice. The uptake mechanism involved the energy-consuming caveolin-mediated endocytosis, and Ce6-AuNR@SiO₂-d-CPP in PTT/PDT mode could induce apoptosis by multiple pathways in breast cancer cells. 
Conclusion: Ce6-AuNR@SiO₂-d-CPP demonstrated a robust efficacy in the treatment of breast cancer by photothermal/photodynamic therapy. Therefore, the present study could offer a new promising strategy to treat the refractory breast cancer.
Keywords: functional chlorin gold nanorods, cell penetrating peptide, PTT/PDT, cellular uptake, cytotoxicity, apoptosis