RESUMEN
Nanoparticles are emerging as a new therapeutic modality due to their high stability, precise targeting, and high biocompatibility. Branched Au-Ag nanoparticles with polydopamine coating (Au-Ag@PDA) have strong near-infrared absorbance and no cytotoxicity but high photothermal conversion efficiency. However, the photothermal activity of Au-Ag@PDA in vivo and in vitro has not been reported yet, and the mechanism underlying the effects of photothermal nanomaterials is not clear. Therefore, in this study, the colorectal cancer cell line HCT-116 and nude mice xenografts were used to observe the photothermal effects of Au-Ag@PDA in vivo and in vitro. The results suggest that Au-Ag@PDA NPs significantly inhibited cell proliferation and induced apoptosis in colorectal cancer cells. Moreover, Au-Ag@PDA NP-mediated photothermal therapy inhibited the growth of tumors at doses of 50 and 100⯵g in vivo. The mechanisms through which Au-Ag@PDA NPs induced colorectal cancer cell death involved multiple pathways, including caspase-dependent and -independent apoptosis, mitochondrial damage, lysosomal membrane permeability, and autophagy. Thus, our findings suggest that Au-Ag@PDA NPs could be used as potential antitumor agents for photothermal ablation of colorectal cancer cells.
Asunto(s)
Apoptosis , Materiales Biocompatibles Revestidos , Neoplasias Colorrectales , Oro , Hipertermia Inducida , Indoles , Nanopartículas del Metal , Fototerapia , Polímeros , Plata , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacocinética , Materiales Biocompatibles Revestidos/farmacología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Oro/química , Oro/farmacocinética , Oro/farmacología , Células HCT116 , Humanos , Indoles/química , Indoles/farmacocinética , Indoles/farmacología , Masculino , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Polímeros/química , Polímeros/farmacocinética , Polímeros/farmacología , Plata/química , Plata/farmacocinética , Plata/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aim of this study is to determine the behavior of relative expression of Bcl-2, caspase-8, caspase-9, and caspase-3 genes of/in SK-MEL-3 cancer cells and explore molecular mechanisms responsible for the apoptosis response during an in vitro photodynamic therapy (PDT) with Zinc Phthalocyanine (ZnPc) using different doses of the light source. In this study, firstly the cytotoxic effects of ZnPc-PDT on SK-MEL-3 cells were evaluated. By irradiating the laser, ZnPc induced a significant amount of apoptosis on SK-MEL-3 cells in three IC50s including 0.064±0.01, 0.043±0.01, and 0.036±0.01µg/mL at the doses of 8, 16, and 24J/cm2, respectively. Moreover, flow cytometry and QRT-PCR experiments were done. The high percentage of apoptotic cells was seen in the early apoptosis stage. The expression of Bcl-2 and caspase-8 genes at all doses of laser experienced an obvious reduction in comparison to the control group. On the other hand, although the expression of caspase-9 and caspase-3 genes remains almost constant at 8J/cm2, but they faced an increment at 16 and 24J/cm2 doses. These data reveal caspase-dependent apoptosis in high and caspase-independent apoptosis in low doses of laser. Based on the results of present work, it can be suggested that the dose of the light source is a key factor in induction of caspase-dependent and caspase-independent apoptosis pathways following PDT.