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Selective Photodynamic Effects on Breast Cancer Cells Provided by p123 Pluronic®- Based Nanoparticles Modulating
Gabrielle Marconi Zago Ferreira Damke1, Raquel Pantarotto Souza1, Maiara Camotti Montanha2
1Department of Clinical Analysis and Biomedicine, Universidade Estadual de Maringa, Parana, Brazil.
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.
Insights
This study shows that supersaturated hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) effectively targets and kills breast cancer cells via photodynamic therapy. HYP/P123 micelles demonstrate potential for preventing recurrence and metastasis, warranting further in vivo evaluation.
Area of Science:
- Biochemistry
- Nanotechnology
- Oncology
Background:
- Breast cancer remains a leading cause of death in women, with a need for novel therapeutic strategies.
- Photodynamic therapy (PDT) offers a promising avenue, but effective drug delivery systems are crucial.
- Previous research explored Pluronics with photosensitizers for PDT.
Purpose of the Study:
- To evaluate the efficacy of supersaturated hypericin (HYP) encapsulated on Pluronic® P123 (HYP/P123) against breast cancer cells.
- To assess the selective toxicity and therapeutic potential of HYP/P123 for breast cancer treatment.
Main Methods:
- Cellular uptake and subcellular localization of HYP/P123 were visualized using fluorescence microscopy.
- Phototoxicity and cytotoxicity were evaluated through trypan blue exclusion and clonogenic assays.
- Cell migration, apoptosis, and necrosis were assessed using wound-healing and Annexin V/PI assays.
Main Results:
- HYP/P123 micelles exhibited high stability and selective internalization into MCF-7 breast cancer cells.
- Accumulation in mitochondria and endoplasmic reticulum led to photodynamic necrosis.
- Effective, dose-dependent phototoxicity was observed in MCF-7 cells with minimal impact on normal breast cells (MCF-10A).
- HYP/P123 inhibited colony formation and tumor cell migration, suggesting potential to prevent recurrence and metastasis.
Conclusions:
- HYP/P123 micelles serve as a promising platform for hypericin delivery in photodynamic therapy for breast cancer.
- The selective targeting and efficacy of HYP/P123 warrant further preclinical investigation in vivo.
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