International Journal of Nanomedicine (Nov 2018)

Functional chlorin gold nanorods enable to treat breast cancer by photothermal/photodynamic therapy

  • Liu L,
  • Xie HJ,
  • Mu LM,
  • Liu R,
  • Su ZB,
  • Cui YN,
  • Xie Y,
  • Lu WL

Journal volume & issue
Vol. Volume 13
pp. 8119 – 8135

Abstract

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Lei Liu,1,* Hong-Jun Xie,2,* Li-Min Mu,1 Rui Liu,1 Zhan-Bo Su,1 Yi-Nuo Cui,1 Ying Xie,1 Wan-Liang Lu1 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China; 2Department of Medicament, College of Medicine, Tibet University, Lhasa, China *These authors contributed equally to this work 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

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