CHLOROALUMINUM PHTHALOCYANINE-GUIDED NANOTHERAPY: A NANOCAPSULES-BASED NANOMEDICINE FOR TARGETED NANO-DRUG DELIVERY IN BREAST CÂNCER THERAPY

Leonardo B. de Paula, Maria A. de Lucca, Maryanne T. de Melo, Antonio C. Tedesco

Department of Chemistry, Center of Nanotechnology and Tissues Engineering Photobiology and Photomedine Research Group, Faculty of Philosophy, Science and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.Introduction: Breast câncer is one of the most common cause of cancer-related death and the second leading incidence of câncer in women. Photodynamic therapy (PDT) is a well-established innovated treatment for tumor due to its high cure rate and low recurrence rate. Objectives: Evaluate the photosensitizer activity combination with PDT in the development of breast câncer. Methodology: We developed the poly(lactic-coglycolic acid) nanocapsules (NC) loaded with chloroaluminum phthalocyanine (ClAlPc) was obtained by a high thermodynamic stability. We compared the different sensitivities between human breast cell lines (MCF-7 and MDA-MB-231) to NC/ClAÍPc-PDT. Cellular responses to NC/ClAÍPc-PDT such as cell viability, cell uptake, DNA fragmentation, cell death mechanism by apoptosis and/or necrosis were examined at different PDT doses. Rcsults: Our findings demonstrate excellent physical and Chemical stability of NC with a size less than 200 nm. The results suggested that the cell uptake was kept at the cytoplasmic levei. Evaluation of the PDT light effects was performed using a diode-laser at doses from 100, 200, 700 and 1000 mJ/cm2. Mitochondrial activity describes a cellular viability of 58% (24 h), 43% (48 h) and 25% (72 h) compared to the absence of activation of the photosensitizer, which is related to the association of the effects of photodamage based on PDT mechanisms and cell injury. All doses tested also resulted in sub-Gl accumulation (20, 24, 55, and 58% at 100, 200, 700 and 1000 mJ/cm2, respectively; p<0.05). Additionally, apoptosis induction was seen as the main cell death pathway in breast câncer cells (total annexin-V positive: 70 and 85% at 700 and 1000 mJ/cm2; respectively; p<0.05). Conclusion: PDT is an appropriate stand alone intervention, or as an adjunct to surgery. This modality causes tissue destruction pathway the interaction between oxygen, light and release of photosensitizing drug nanoentrapped.photodynamic therapy, photosensitizer, cell death.