RESUMEN
Organic semiconductor small molecules IHIC and ITIC have been developed as solar cell materials, and because of their strong near-infrared absorption capabilities, they are promising for cancer phototherapy. This article reports the application of semiconductor small molecule IHIC/ITIC liposomes in photothermal therapy and photoacoustic imaging of tumors firstly. Experiments show that the liposome-loaded IHIC/ITIC material has good biocompatibility and can be effectively enriched in tumor sites. After being irradiated with laser, it can emit strong photoacoustic signals, and has achieved good results in the photothermal treatment of breast cancer mice. We believe that organic semiconductor small molecule IHIC/ITIC will become a promising photothermal agent with wonderful development possibilities.
Asunto(s)
Materiales Biocompatibles/química , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Semiconductores , Animales , Materiales Biocompatibles/metabolismo , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Endocitosis/efectos de los fármacos , Endocitosis/efectos de la radiación , Células HeLa , Humanos , Rayos Láser , Liposomas/química , Ratones , Ratones Desnudos , Microscopía Confocal , Neoplasias/diagnóstico por imagen , Neoplasias/patología , Tamaño de la Partícula , Técnicas Fotoacústicas , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/metabolismo , Fármacos Fotosensibilizantes/farmacología , Terapia Fototérmica , Trasplante HeterólogoRESUMEN
A novel coreshell type thermonanoparticle (CSTNP) coloaded with temozolomide (TMZ) and the fluorescein new indocyanine green dye IR820 (termed ITCSTNPs) was designed and combined with a nearinfrared (NIR) laser to realize its photothermal conversion. The ITCSTNPs were prepared using a twostep synthesis method and comprised a thermosensitive shell and a biodegradable core. IR820 and TMZ were entrapped in the shell and the core, respectively. Dynamic light scattering results demonstrated that the average hydrodynamic size of the ITCSTNPs was 196.4±3.1 nm with a ζ potential of 24.9±1.3 mV. The encapsulation efficiencies of TMZ and IR820 were 6.1 and 16.6%, respectively. Temperature increase curves under NIR laser irradiation indicated that the ITCSTNPs exhibited the desired photothermal conversion efï¬ciency. The in vitro drug release curves revealed a suitable release capability of ITCSTNP under physiological conditions, whereas NIR laser irradiation accelerated the drug release. Inverted fluorescence microscopy and flow cytometry results revealed that the uptake of ITCSTNPs by A375 melanoma cells occurred in a concentrationdependent manner. Confocal laser scanning microscopy results indicated that ITCSTNPs entered tumour cells via endocytosis and were located in intercellular lysosomes. In summary, the present study explored the photothermal conversion capability, cellular uptake, and intracellular localization of ITCSTNPs.
Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Portadores de Fármacos/química , Hipertermia Inducida/métodos , Melanoma/terapia , Neoplasias Cutáneas/terapia , Temozolomida/administración & dosificación , Antineoplásicos Alquilantes/farmacocinética , Línea Celular Tumoral , Terapia Combinada/métodos , Portadores de Fármacos/efectos de la radiación , Liberación de Fármacos/efectos de la radiación , Dispersión Dinámica de Luz , Endocitosis/efectos de la radiación , Humanos , Hipertermia Inducida/instrumentación , Verde de Indocianina/administración & dosificación , Verde de Indocianina/análogos & derivados , Rayos Láser , Melanoma/patología , Nanopartículas/química , Nanopartículas/efectos de la radiación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Neoplasias Cutáneas/patología , Temozolomida/farmacocinéticaRESUMEN
Light exposure modulates development of living organisms. In the field of medicine, light has frequently been used for regenerative purposes. Excimer light (308 nm) has demonstrated superior efficacy in treating vitiligo, a condition requiring development of melanoblasts and a model for studying nerve cell regeneration, as compared to narrow-band ultraviolet B (NBUVB; 311 nm). Using mouse-derived melanoblast cells to examine the pro-differentiation effects of these two light sources, we demonstrated that at equivalent fluence, excimer light induces melanoblast differentiation, while NBUVB failed to so. Mechanistically, activation of aryl hydrocarbon receptor pathway and nuclear translocation of epidermal growth factor receptor are involved in pro-differentiation effects of excimer light. Reduction in irradiance by filter abrogated the effects of excimer light in melanoblasts, even when equivalent fluence was delivered by the same light source. As ultraviolet B (UVB) irradiation is closely associated pigment cell development, future therapy employing UVB for pigmentation purposes should incorporate irradiance as a crucial specification.
Asunto(s)
Diferenciación Celular/efectos de la radiación , Melanocitos/citología , Melanocitos/efectos de la radiación , Pigmentación/efectos de la radiación , Rayos Ultravioleta , Terapia Ultravioleta , Animales , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de la radiación , Inmunoprecipitación de Cromatina , Citocromo P-450 CYP1A1/biosíntesis , Citocromo P-450 CYP1A1/genética , Endocitosis/efectos de la radiación , Inducción Enzimática/efectos de la radiación , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de la radiación , Silenciador del Gen/efectos de la radiación , Inmunohistoquímica , Melanocitos/enzimología , Ratones , Monofenol Monooxigenasa/biosíntesis , Monofenol Monooxigenasa/genética , Regiones Promotoras Genéticas/genética , Transporte de Proteínas/efectos de la radiación , Dímeros de Pirimidina/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Hidrocarburo de Aril/genética , Receptores de Hidrocarburo de Aril/metabolismo , Transcripción Genética/efectos de la radiación , Familia-src Quinasas/metabolismoRESUMEN
Single-walled carbon nanotubes (SWNTs) are special nano-materials which exhibit interesting physical and chemical properties, presenting new opportunities for biomedical research and applications. In this study, we have successfully adopted a novel strategy to chemically functionalize SWNTs with polyethylenimine (PEI) through purification, oxidation, amination and polymerization, which were then bound by DSPE-PEG2000-Maleimide for further conjugation with the tumor targeting NGR (Cys-Asn-Gly-Arg-Cys-) peptide via the maleimide group and sulfhydryl group of cysteine, and finally hTERT siRNA was loaded to obtain a novel tumor targeting siRNA delivery system, designated as SWNT-PEI/siRNA/NGR. The results showed that SWNT-PEI/siRNA/NGR could efficiently cross cell membrane, induced more severe apoptosis and stronger suppression in proliferation of PC-3 cells in vitro. Furthermore, in tumor-bearing mice model the delivery system exhibited higher antitumor activity due to more accumulation in tumor without obvious toxicity in main organs. The combination of RNAi and near-infrared (NIR) photothermal therapy signiï¬cantly enhanced the therapeutic efï¬cacy. In conclusion, SWNT-PEI/siRNA/NGR is a novel and promising anticancer system by combining gene therapy and photothermal therapy.