RESUMEN
Poor tumor selectivity, low stability and quenched fluorescence are the main challenges to be overcome for nanomedicine, and are mainly caused by the dissociation of the nanostructure and aggregation of chromophores in the biological environment. Herein, covalently connected nanoparticles RGD-graphene-phthalocyanine (RGD-GO-SiPc) were constructed based on RGD peptide, silicon phthalocyanine (SiPc) and graphene oxide (GO) via a conjugation reaction for fluorescence imaging-guided cancer-targeted combinatorial phototherapy. The prepared RGD-GO-SiPc exhibited supreme biological stability, high-contrast fluorescence imaging, significantly enhanced NIR absorption, high photothermal conversion efficiency (25.6%), greatly improved cancer-targeting capability, and synergistic photodynamic (PDT) and photothermal therapy (PTT) efficacy along with low toxicity. Both in vitro and in vivo biological studies showed that RGD-GO-SiPc is a kind of promising multifunctional nanomedicine for fluorescence imaging-guided combined photothermal and photodynamic therapy with dual active/passive tumor-targeting properties.
Asunto(s)
Antineoplásicos/uso terapéutico , Colorantes Fluorescentes/uso terapéutico , Nanocompuestos/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Femenino , Colorantes Fluorescentes/química , Colorantes Fluorescentes/efectos de la radiación , Grafito/química , Grafito/efectos de la radiación , Grafito/uso terapéutico , Células HEK293 , Humanos , Isoindoles/química , Isoindoles/efectos de la radiación , Isoindoles/uso terapéutico , Luz , Ratones , Nanocompuestos/química , Nanocompuestos/efectos de la radiación , Nanopartículas/química , Nanopartículas/efectos de la radiación , Nanopartículas/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/metabolismo , Oligopéptidos/química , Imagen Óptica , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/efectos de la radiación , Fármacos Fotosensibilizantes/uso terapéutico , Fototerapia , Oxígeno Singlete/metabolismoRESUMEN
X-ray induced molecular luminescence (XML) is a phenomenon that can be utilized for clinical, deep-tissue functional imaging of tailored molecular probes. In this study, a survey of common or clinically approved fluorophores was carried out for their megavoltage X-ray induced excitation and emission characteristics. We find that direct scintillation effects and Cherenkov generation are two possible ways to cause these molecules' excitation. To distinguish the contributions of each excitation mechanism, we exploited the dependency of Cherenkov radiation yield on X-ray energy. The probes were irradiated by constant dose of 6 MV and 18 MV X-ray radiation, and their relative emission intensities and spectra were quantified for each X-ray energy pair. From the ratios of XML, yield for 6 MV and 18 MV irradiation we found that the Cherenkov radiation dominated as an excitation mechanism, except for aluminum phthalocyanine, which exhibited substantial scintillation. The highest emission yields were detected from fluorescein, proflavin and aluminum phthalocyanine, in that order. XML yield was found to be affected by the emission quantum yield, overlap of the fluorescence excitation and Cherenkov emission spectra, scintillation yield. Considering all these factors and XML emission spectrum respective to tissue optical window, aluminum phthalocyanine offers the best XML yield for deep tissue use, while fluorescein and proflavine are most useful for subcutaneous or superficial use.