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

Autor: Ludmilla David de Moura, Leonardo G. Paterno, Mayara Simonelly Costa dos Santos, Fabiane H. Veiga-Souza, Emanuel Adelino Medeiros Damasceno, Sônia Nair Báo, Ricardo Bentes Azevedo, Ana Luisa Gouvêa, Ana Paula Bastos, Paulo Eduardo Narcizo de Souza
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Ablation Techniques
Luminescence
medicine.medical_treatment
Cell
Pharmaceutical Science
Medicine (miscellaneous)
Photodynamic therapy
Apoptosis
02 engineering and technology
01 natural sciences
Applied Microbiology and Biotechnology
Metastasis
Tumor regression and metastasis avoidance
chemistry.chemical_compound
Mice
Photosensitizer
Neoplasm Metastasis
Graphene oxide
Mice
Inbred BALB C
021001 nanoscience & nanotechnology
Immunohistochemistry
Photothermal therapy
Tumor Burden
medicine.anatomical_structure
lcsh:R855-855.5
Molecular Medicine
Female
Graphite
Bioluminescence
0210 nano-technology
Methylene blue
lcsh:Medical technology
Cell Survival
lcsh:Biotechnology
Biomedical Engineering
Bioengineering
Mammary Neoplasms
Animal
010402 general chemistry
In vivo
Cell Line
Tumor
lcsh:TP248.13-248.65
medicine
Photosensitizer dye
Animals
Cell damage
Research
Body Weight
Phototherapy
medicine.disease
0104 chemical sciences
Methylene Blue
Disease Models
Animal
chemistry
Photochemotherapy
Cancer research
NIH 3T3 Cells
Nanoparticles
Reactive Oxygen Species
Zdroj: Journal of Nanobiotechnology, Vol 16, Iss 1, Pp 1-17 (2018)
Journal of Nanobiotechnology
ISSN: 1477-3155
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12951-018-0333-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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