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Application of biophotonics in the analyses of the photosensitizers isoquinoline alkaloids berberine e isomoschatoline interaction with LDL in cell models

Grant number: 11/23031-3
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): July 01, 2012
Effective date (End): June 30, 2013
Field of knowledge:Health Sciences - Pharmacy - Pharmacognosy
Principal Investigator:Marcos José Salvador
Grantee:Nathalia Luiza Andreazza
Supervisor: Stéphanie Bonneau
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: Université Pierre et Marie Curie (Paris 6), France  


The use of nontoxic dyes or photosensitizers (PS) in combination with non-harmful visible light in medicine, called Photodynamic Therapy, is known to more than 100 years, however, only now it has been widely used to treat infectious diseases and cancers. Previous analyses of absorption and fluorescence spectroscopy of isoquinoline alkaloids berberine and isomoschatolina have revealed their potential as photosensitizing agents. Promising results was observed in the application of these compounds in antitumor PDT with significant reduction of tumor cell growth of human melanoma UACC-62. Since the incorporation and subcellular localization of the PS are critical determinants of its effectiveness, a more detailed experimental approach, to assist the elucidation of these parameters is necessary. Furthermore, several studies have found that the complexation of photosensitizers with LDL (low-density lipoproteins) increased their internalization by cancer cells, since an increase in apo B receptor expression is observed on the cell surface responsible for the internalization of LDL because of high rates of cancer cells proliferation. Within this context, looking for a greater depth of study from an approach at the cellular level, we established a partnership with the Laboratoire Jean Perrin, CNRS FRE 3231, Université Pierre et Marie Curie, Paris, France in particular with the Prof. Dr. Stéphanie Bonneau, due to her vast experience in understanding the interactions of PS with LDL and cell membranes and cellular incorporation on the photomodulation and biophysics of membranes and intracellular trafficking. In this project, it is proposed to study the interaction of these alkaloids with the LDL in cell models. We intent to characterize the spectroscopic properties and the binding chemistry of complexes formed between berberine and isomoschatolina with LDL, looking to determine the maximum saturation level for the complexiation between the monomeric alkaloids and LDL, as well as, compare the profiles of absorption and fluorescence of these complexes alone or with LDL. In the model cell cultures of human fibroblasts, strain HS68, it is intent to assess whether the complexation of alkaloids with LDL increases its absorption by the cells, seeking to characterize the absorption kinetics of the complexes, as well as determine the intracellular localization of these alkaloids. Techniques such as fluorescence spectroscopy, flow cytometry and confocal laser fluorescence will be used to the develop of this study. This work could contribute to the development of a new vectorization system of the alkaloids berberine and isomoschatolina to ensure better absorption by the cells and greater efficiency in PDT, allowing the administration of small doses of the compounds, avoiding possible side effects due to toxicity. The study also will bring more information to enrich the discussion about the potential of LDL as a carrier of photosensitizers in the human body and as a delivery- molecule to the specific accumulation of these drugs in tumor tissues. It will also contribute to the progress that has been achieved in the study of PDT, both in basic science and in clinical photodynamic, a promising technology for the topical treatment of infections, inflammation and cancer, in order to obtain new materials and technologies for application in the pharmaceutical area (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ANDREAZZA, NATHALIA LUIZA; VEVERT-BIZET, CHRISTINE; BOURG-HECKLY, GENEVIEVE; SUREAU, FRANCK; SALVADOR, MARCOS JOSE; BONNEAU, STEPHANIE. Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins. International Journal of Pharmaceutics, v. 510, n. 1, p. 240-249, . (11/23031-3)

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