RESUMO
Metal nanoparticles have significant interaction cross-sections with electromagnetic waves due to their large surface area-to-volume ratio, which can be exploited in cancer radiotherapy to locally enhance the radiation dose deposition in tumors. We developed a new type of silver nanoparticle composite, PEGylated graphene quantum dot (GQD)-decorated Silver Nanoprisms (pGAgNPs), that show excellent in vitro intracellular uptake and radiosensitization in radiation-sensitive HCT116 and relatively radiation-resistant HT29 colorectal cancer cells. Furthermore, following biodistribution analysis of intravenously injected nanoparticles in nude mice bearing HCT116 tumors radiosensitization was evaluated. Treatment with nanoparticles and a single radiation dose of 10 Gy significantly reduces the growth of colorectal tumors and increases the survival time as compared to treatment with radiation only. Our findings suggest that these novel nanoparticles offer a promising paradigm for enhancing colorectal cancer radiation therapy efficacy.
Assuntos
Neoplasias Colorretais/radioterapia , Grafite/química , Nanopartículas Metálicas/administração & dosagem , Radiossensibilizantes/administração & dosagem , Prata/química , Animais , Apoptose , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Raios gama , Humanos , Masculino , Nanopartículas Metálicas/química , Camundongos , Pontos Quânticos , Radiossensibilizantes/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The combination of chemotherapy and photodynamic therapy has emerged as a promising strategy for cancer therapy due to its synergistic effects. In this work, PEGylated silver nanoparticles decorated with graphene quantum dots (Ag-GQDs) were tested as a platform to deliver a chemotherapy drug and a photosensitizer, simultaneously, in chemo-photodynamic therapy against HeLa and DU145 cancer cells in vitro. Ag-GQDs have displayed high efficiency in delivering doxorubicin as a model chemotherapy drug to both cancer cells. The Ag-GQDs exhibited a strong antitumor activity by inducing apoptosis in cancer cells without affecting the viability of normal cells. Moreover, the Ag-GQDs exhibited a cytotoxic effect due to the generation of the reactive singlet oxygen upon 425 nm irradiation, indicating their applicability in photodynamic therapy. In comparison with chemo or photodynamic treatment alone, the combined treatment of Ag-GQDs conjugated with doxorubicin under irradiation with a 425 nm lamp significantly increased the death in DU145 and HeLa. This study suggests Ag-GQDs as a multifunctional and efficient therapeutic system for chemo-photodynamic modalities in cancer therapy.
Assuntos
Antineoplásicos/farmacologia , Nanocompostos , Fotoquimioterapia/métodos , Pontos Quânticos , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Terapia Combinada/métodos , Doxorrubicina/química , Doxorrubicina/farmacologia , Quimioterapia Combinada , Grafite/química , Grafite/farmacologia , Células HeLa/efeitos dos fármacos , Humanos , Nanocompostos/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Pontos Quânticos/uso terapêutico , Prata/química , Prata/farmacologia , Oxigênio Singlete/metabolismoRESUMO
Graphene has been the subject of intense research in recent years due to its unique electrical, optical and mechanical properties. Furthermore, it is expected that quantum dots of graphene would make their way into devices due to their structure and composition which unify graphene and quantum dots properties. Graphene quantum dots (GQDs) are planar nano flakes with a few atomic layers thick and with a higher surface-to-volume ratio than spherical carbon dots (CDs) of the same size. We have developed a pulsed laser synthesis (PLS) method for the synthesis of GQDs that are soluble in water, measure 2-6 nm across, and are about 1-3 layers thick. They show strong intrinsic fluorescence in the visible region. The source of fluorescence can be attributed to various factors, such as: quantum confinement, zigzag edge structure, and surface defects. Confocal microscopy images of bacteria exposed to GQDs show their suitability as biomarkers and nano-probes in high contrast bioimaging.