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1.
Int J Pharm ; 554: 93-104, 2019 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-30385376

RESUMO

The combination of photothermal therapy and targeted chemotherapy can produce much greater cytotoxicity than chemotherapy. Herein, we developed multifunctional targeted polymeric nanoparticles (NPs) loaded with indocyanine green (ICG) and doxorubicin (DOX) for the targeted photoacoustic imaging and photothermal ablation of oral cancer cells. The chemokine SDF-1, a specific antibody, was conjugated to NPs by the carbodiimide method. The NPs were automatically targeted to tumour tissue in vitro and in vivo through CXCR4-SDF-1 interactions. The results of in vivo and in vitro photoacoustic imaging and photothermal therapy experiments showed that the multifunctional NPs had excellent photoacoustic imaging characteristics and photothermal therapy capabilities. The photothermal material heated rapidly after laser irradiation, and the resulting heat increased cell metabolism and membrane permeability, which increased cellular NP uptake. The encapsulated drug (DOX) was released immediately after the liquid core was transformed into a gas via laser effects, which killed tumour cells while producing strong photoacoustic signals in vitro and in vivo. Thus, we concluded that the chemokine SDF-1 can be applied for the targeted chemotherapy of metastatic lymph nodes of oral squamous cell carcinoma (OSCC) and is more effective for treating oral cancer when combined with photothermal therapy than when used alone.


Assuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Quimiocina CXCL12/administração & dosagem , Nanopartículas , Técnicas Fotoacústicas/métodos , Neoplasias da Língua/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Verde de Indocianina/administração & dosagem , Verde de Indocianina/química , Metástase Linfática/diagnóstico por imagem , Masculino , Fototerapia/métodos , Polímeros/química , Coelhos , Neoplasias da Língua/diagnóstico por imagem
2.
Ann Thorac Surg ; 78(3): 970-5, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15337030

RESUMO

BACKGROUND: We examined the effects of pinacidil on contractile function and intracellular calcium in isolated rat cardiomyocytes exposed to cardioplegic solution. METHODS: Rat myocytes were incubated at 24 degrees C for 2 hours in cardioplegic solution with or without pinacidil (50 micromol/L), then they were perfused with Krebs-Henseleit solution with a gas phase of 95% O2/5% CO2 at the same temperature. Contraction and intracellular calcium transients were then measured by video tracking and spectrofluorometry. RESULTS: During 20 minutes of perfusion after 2 hours in cardioplegic solution with pinacidil, (1) the recovery of contractile function was significantly increased in terms of both amplitude of contraction (98.30% +/- 9.90% versus 81.00% +/- 11.25%; p < 0.05) and peak velocity of cell shortening (100.90% +/- 13.79% versus 76.89% +/- 18.14%; p < 0.01) when compared with myocytes in cardioplegic solution without pinacidil; (2) the amplitudes of the intracellular calcium transients evoked by electrical stimulation and caffeine (10 mmol/L) increased by 23.31% to approximately 40.72% and 61.73%, respectively, compared with those in cardioplegic solution without pinacidil; and (3) the decay time of the caffeine-induced intracellular calcium transient decreased by 36.64% +/- 15.10% relative to that measured in cardioplegic solution without pinacidil. The effects induced by supplementing the cardioplegic solution with pinacidil were diminished in the presence of glibenclamide (10 micromol/L). CONCLUSIONS: Addition of the adenosine triphosphate-sensitive potassium-channel opener, pinacidil, to a high potassium cardioplegic solution improves recovery of contractile properties and cytosolic calcium in isolated rat cardiac myocytes.


Assuntos
Cálcio/metabolismo , Células Musculares/metabolismo , Contração Miocárdica/efeitos dos fármacos , Pinacidil/farmacologia , Animais , Agonistas dos Canais de Cálcio/farmacologia , Células Cultivadas , Parada Cardíaca Induzida , Masculino , Células Musculares/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Retículo Sarcoplasmático/metabolismo , Trocador de Sódio e Cálcio/metabolismo , Vasoconstritores/farmacologia
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