Gabrielle Marconi Zago Ferreira Damke
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Raquel Pantarotto Souza
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Maiara Camotti Montanha
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Edilson Damke
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Renato Sonchini Gonçalves
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...
Background:
Breast cancer is the most relevant type of cancer and the second cause of cancer- related
deaths among women in general. Currently, there is no effective treatment for breast cancer although advances
in its initial diagnosis and treatment are available. Therefore, the value of novel anti-tumor therapeutic
modalities remains an immediate unmet need in clinical practice. Following our previous work regarding the
properties of the Pluronics with different photosensitizers (PS) for photodynamic therapy (PDT), in this study
we aimed to evaluate the efficacy of supersaturated hypericin (HYP) encapsulated on Pluronic® P123
(HYP/P123) against breast cancer cells (MCF-7) and non-tumorigenic breast cells (MCF-10A).
Methods:
Cell internalization and subcellular distribution of HYP/P123 was confirmed by fluorescence microscopy.
The phototoxicity and citototoxicity of HYP/P123 was assessed by trypan blue exclusion assay in the
presence and absence of light. Long-term cytotoxicity was performed by clonogenic assay. Cell migration was
determined by the wound-healing assay. Apoptosis and necrosis assays were performed by annexin VFITC/
propidium Iodide (PI) by fluorescence microscopy.
Results:
Our results showed that HYP/P123 micelles had high stability and high rates of binding to cells, which
resulted in the selective internalization in MCF-7, indicating their potential to permeate the membrane of these
cells. Moreover, HYP/P123 micelles accumulated in mitochondria and endoplasmic reticulum organelles, resulting
in the photodynamic cell death by necrosis. Additionally, HYP/P123 micelles showed effective and selective
time- and dose dependent phototoxic effects on MCF-7 cells but little damage to MCF-10A cells. HYP/P123
micelles inhibited the generation of cellular colonies, indicating a possible capability to prevent the recurrence
of breast cancer. We also demonstrated that HYP/P123 micelles inhibit the migration of tumor cells, possibly by
decreasing their ability to form metastases.
Conclusion:
Taken together, the results presented here indicate a potentially useful role of HYP/P123 micelles
as a platform for HYP delivery to more specifically and effectively treat human breast cancers through photodynamic
therapy, suggesting they are worthy for in vivo preclinical evaluations.
Photodynamic activity of Sn(IV) meso-tetraacenaphthylporphyrin and its methyl-β-cyclodextrin inclusion complexes on MCF-7 breast cancer cells
