کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3818236 | 1246362 | 2014 | 16 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Polymeric micelles for enhanced Photofrin II® delivery, cytotoxicity and pro-apoptotic activity in human breast and ovarian cancer cells Polymeric micelles for enhanced Photofrin II® delivery, cytotoxicity and pro-apoptotic activity in human breast and ovarian cancer cells](/preview/png/3818236.png)
• Polymeric micelles of P123 and F127 significantly enhance photodynamic effect with Photofrin II®.
• Polymeric micelles efficiently deliver photosensitizer in SKOV-3 and MCF-7/WT cells.
• PDT with Photofrin II® loaded in polymeric micelles induces with low hemolytic impact.
SummaryBackgroundSearching for photodynamic therapy (PDT) – effective nanocarriers which enable a photosensitizer to be selectively delivered to tumor cells with enhanced bioavailability and diminished dark cytotoxicity is of current interest. The main objective of this study is to evaluate newly designed mixed polymeric micelles based on Pluronics P123 and F127 for the improved delivery of Photofrin II® (Ph II®) to circumvent unfavorable effects overcoming multidrug resistance (MDR) in tumor cells – in breast MCF-7/WT (caspase-3 deficient) and ovarian SKOV-3 (resistant to chemotherapy).MethodsPh II®-loaded micelles were obtained and analyzed for size and morphology, solubilization efficiency, physical stability and in vitro drug release. Intracellular uptake, reactive oxygen species (ROS) generation, mitochondrial oxidoreductive potential and proapoptotic activity (TUNEL assay) studies were evaluated in the examined cancer cells. The preliminary biocompatibility characteristics of all nanocarriers was determined by assessment of their hemolytic activity in human erythrocytes and dark toxicity in cancer cells.ResultsDynamic light scattering (DLS) and atomic force microscopy (AFM) confirmed that almost monodisperse, sphere-shaped and nanosized (DH < 20 nm) carriers were developed. Biological studies after photodynamic reaction (PDR) with encapsulated Ph II® revealed increased ROS level, malondialdehyde (MDA) concentration and protein damage in SKOV-3 and MCF-7/WT cells in comparison to treatment with free Ph II®. Numerous apoptotic cells were detected after nano-therapy in both cell lines, with observed significant morphological disorders in ovarian cancer cells. In the case of encapsulated Ph II® only negligible disruption of human erythrocytes and cancer cells was observed.ConclusionsThe obtained biocompatible long-lasting nanocarriers significantly enhance the Photofrin II® photodynamic effect and apoptosis in both SKOV-3 and MCF-7/WT cell lines.
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Journal: Photodiagnosis and Photodynamic Therapy - Volume 11, Issue 4, December 2014, Pages 570–585