Nanographene oxide-methylene blue as phototherapies platform for breast tumor ablation and metastasis prevention in a syngeneic orthotopic murine model

Journal of Nanobiotechnology

Ana Luisa Gouvêa¹  Mayara Simonelly Costa dos Santos¹  Sônia Nair Báo¹  Ana Paula Bastos²  Leonardo Giordano Paterno³  Paulo Eduardo Narcizo de Souza⁴  Ludmilla David de Moura⁵  Ricardo Bentes de Azevedo⁵  Emanuel Adelino Medeiros Damasceno⁶  Fabiane Hiratsuka Veiga-Souza⁷ 

[1] Electron Microscopy Laboratory, Institute of Biological Sciences, University of Brasilia;Embrapa Pigs and Poultry, Brazilian Agricultural Research Corporation;Laboratory of Research on Polymers and Nanomaterials, University of Brasilia;Laboratory of Software and Instrumentation in Applied Physics and Laboratory of Electron Paramagnetic Resonance, Institute of Physics, University of Brasilia;Nanobiotechnology Laboratory, Institute of Biological Sciences, University of Brasilia;Nucleus of Pathological Anatomy, Regional Hospital of Taguatinga;School of Ceilandia, University of Brasilia;

关键词: Photodynamic therapy;    Photothermal therapy;    Graphene oxide;    Photosensitizer dye;    Bioluminescence;    Tumor regression and metastasis avoidance;   

DOI  :  10.1186/s12951-018-0333-6

来源: DOAJ

【 摘 要 】

Abstract Background In the photodynamic therapy (PDT), the photosensitizer absorbs light and transfers the energy of the excited state to the oxygen in the cell environment producing reactive oxygen species (ROS), that in its turn, may cause cell damage. In the photothermal therapy (PTT), light also is responsible for activating the photothermal agent, which converts the absorbed energy in heat. Graphene oxide is a carbon-based material that presents photothermal activity. Its physical properties allow the association with the photosensitizer methylene blue and consequently the production of ROS when submitted to light irradiation. Therefore, the association between nanographene oxide and methylene blue could represent a strategy to enhance therapeutic actions. In this work, we report the nanographene oxide-methylene blue platform (NanoGO-MB) used to promote tumor ablation in combination with photodynamic and photothermal therapies against a syngeneic orthotopic murine breast cancer model. Results In vitro, NanoGO-MB presented 50% of the reactive oxygen species production compared to the free MB after LED light irradiation, and a temperature increase of ~ 40 °C followed by laser irradiation. On cells, the ROS production by the nanoplatform displayed higher values in tumor than normal cells. In vivo assays demonstrated a synergistic effect obtained by the combined PDT/PTT therapies using NanoGO-MB, which promoted complete tumor ablation in 5/5 animals. Up to 30 days after the last treatment, there was no tumor regrowth compared with only PDT or PTT groups, which displayed tumoral bioluminescence 63-fold higher than the combined treatment group. Histological studies confirmed that the combined therapies were able to prevent tumor regrowth and liver, lung and spleen metastasis. In addition, low systemic toxicity was observed in pathologic examinations of liver, spleen, lungs, and kidneys. Conclusions The treatment with combined PDT/PTT therapies using NanoGO-MB induced more toxicity on breast carcinoma cells than on normal cells. In vivo, the combined therapies promoted complete tumor ablation and metastasis prevention while only PDT or PTT were unable to stop tumor development. The results show the potential of NanoGO-MB in combination with the phototherapies in the treatment of the breast cancer and metastasis prevention.

【 授权许可】

Unknown