Conjugação de nanopartículas superparamagnéticas de óxido de ferro e curcumina: associação da terapia fotodinâmica e hipertermia magnética
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Data
2019-05-07
Autores
Santana, Willian Max Oliveira de Souza de
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Universidade Estadual Paulista (Unesp)
Resumo
A incidência de infecções cutâneas causadas por agentes bacterianos resistentes ao tratamento convencional com antibióticos tornou-se um grande problema de saúde pública. Algumas abordagens terapêuticas alternativas têm sido propostas, dentre elas a terapia fotodinâmica antimicrobiana (aPDT) e hipertermia magnética (HM). A aPDT envolve a geração de espécies reativas de oxigênio (EROs) por meio da combinação de luz, oxigênio molecular e um agente fotossensibilizador (FS), e a HM promove o aumento da temperatura de uma região anatômica submetendo nanopartículas superparamagnéticas de óxido de ferro (SPIONPs) a um campo magnético alternado (CMA). O FS de escolha para este estudo foi a curcumina (CUR), muito usado em aPDT, porém tem a fotoavidade fortemente afetada em meios aquosos devido à tendência a agregação. Visando evitar isto, além de promover a melhoria da administração da CUR e a combinação de aPDT e HM num único material foi proposto neste trabalho a síntese de conjugados SPIONP-curcumina (Magh-CUR), assim como a sua avaliação em aPDT e HM contra Staphylococcus aureus em fase planctônica. Este material magnético foi preparado por uma metodologia de coprecipitação alcalina seguida por uma etapa de conjugação com a CUR. Os conjugados foram caracterizados por difração de raios X, microscopia eletrônica de transmissão, potencial zeta, espectroscopia no infravermelho com transformada de Fourier, termogravimetria, magnetometria e ensaios de HM. Os resultados evidenciaram que as nanopartículas de Magh-CUR obtidas apresentaram morfologia esferoidal e tamanho médio de ~ 15 nm e que a conjugação de CUR se dá por interações fracas e por ligações entre o grupo ceto- enol da CUR com os íons de ferro presentes na superfície das SPIONPs. Além disso, os conjugados apresentaram poder de aquecimento sob CMA e ação fotodinâmica quando irradiados com luz de LEDs azul. Nos experimentos microbiológicos de aPDT foi demonstrado que o conjugado consegue promover redução total da carga bacteriana numa dose de luz de 3,12 J.cm-2. Os ensaios de liberação in vitro dos conjugados evidenciaram que a liberação de CUR foi dependente da temperatura. Desta forma, os conjugados Magh-CUR se mostraram promissores para aplicações biológicas, pois permitem associar a aPDT com HM e nanocarreamento da CUR num mesmo sistema.
The incidence of cutaneous infections caused by bacteria resistant to conventional antibiotic treatment has become a major public health problem. Some alternative therapeutic approaches have been proposed, among them antimicrobial photodynamic therapy (aPDT) and magnetic hyperthermia (MH). The aPDT involves the generation of reactive oxygen species (ROS) by using the combination of light, molecular oxygen and a photosensitizing agent (PS), and MH promotes temperature increase of an anatomic region by subjecting superparamagnetic iron oxide nanoparticles (SPIONPs) to an alternating magnetic field (AMF). The PS of choice for this study was curcumin (CUR), widely used in aPDT, but still has its photoactivity strongly affected in aqueous media due to the tendency of aggregation. In order to solve this problem and to promote the improvement of the administration of CUR, we propose the combination of CUR and SPIONPs of maghemite in a single material. Therefore, the objective of this work was to synthesize a SPIONPs-curcumin conjugate (Magh-CUR) and, mediated by the aPDT, to evaluate it against Staphylococcus aureus in the planktonic phase. This magnetic material was prepared by an alkaline coprecipitation method followed by a conjugation step with CUR. The conjugates were characterized by X-ray diffraction, electron transmission microscopy, zeta potential, infrared spectroscopy with Fourier transform, thermogravimetry, magnetometry, MH assays. The characterizations showed that the Magh-CUR had spheroid forms with sizes of ~ 15 nm and the conjugation was due to strong interactions between the CUR keto-enol group and the iron ions on the surface of the SPIONPs. In addition, the conjugates showed high heating power under CMA and photodynamic action when irradiated with blue LEDs light. In the microbiological experiments of aPDT it was shown that the conjugate can promote total reduction of the bacterial load in a low dose of light. The in vitro release assays of the conjugates showed that the release of CUR was dependent on temperature. In this way, the Magh-CUR conjugates are interesting materials for biological applications, since they allow to associate the aPDT with MH and drug delivery of the CUR in the same material.
The incidence of cutaneous infections caused by bacteria resistant to conventional antibiotic treatment has become a major public health problem. Some alternative therapeutic approaches have been proposed, among them antimicrobial photodynamic therapy (aPDT) and magnetic hyperthermia (MH). The aPDT involves the generation of reactive oxygen species (ROS) by using the combination of light, molecular oxygen and a photosensitizing agent (PS), and MH promotes temperature increase of an anatomic region by subjecting superparamagnetic iron oxide nanoparticles (SPIONPs) to an alternating magnetic field (AMF). The PS of choice for this study was curcumin (CUR), widely used in aPDT, but still has its photoactivity strongly affected in aqueous media due to the tendency of aggregation. In order to solve this problem and to promote the improvement of the administration of CUR, we propose the combination of CUR and SPIONPs of maghemite in a single material. Therefore, the objective of this work was to synthesize a SPIONPs-curcumin conjugate (Magh-CUR) and, mediated by the aPDT, to evaluate it against Staphylococcus aureus in the planktonic phase. This magnetic material was prepared by an alkaline coprecipitation method followed by a conjugation step with CUR. The conjugates were characterized by X-ray diffraction, electron transmission microscopy, zeta potential, infrared spectroscopy with Fourier transform, thermogravimetry, magnetometry, MH assays. The characterizations showed that the Magh-CUR had spheroid forms with sizes of ~ 15 nm and the conjugation was due to strong interactions between the CUR keto-enol group and the iron ions on the surface of the SPIONPs. In addition, the conjugates showed high heating power under CMA and photodynamic action when irradiated with blue LEDs light. In the microbiological experiments of aPDT it was shown that the conjugate can promote total reduction of the bacterial load in a low dose of light. The in vitro release assays of the conjugates showed that the release of CUR was dependent on temperature. In this way, the Magh-CUR conjugates are interesting materials for biological applications, since they allow to associate the aPDT with MH and drug delivery of the CUR in the same material.
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Palavras-chave
Staphylococcus aureus, Óxido de ferro, Curcumina, Photochemotherapy, Fotoquimioterapia, Iron oxide, Curcumin, Thermotherapy, Termoterapia