RESUMEN
Therapeutic effects of hybrid liposomes (L-α-dimyristoylphosphatidylcholine (DMPC)/docosahexaenoic acid (DHA)) composed of 50 mol% DMPC and 50 mol% DHA on the metastasis of human colon carcinoma (HCT116) cells were examined in vivo. DMPC/DHA having a hydrodynamic diameter less than 100 nm were preserved for one month. Remarkably high therapeutic effects were obtained in the hepatic metastasis mouse models of HCT116 cells after the intravenous injection of DMPC/DHA. The histological analysis indicated the induction of apoptosis was observed in the liver section of the hepatic metastasis mouse models treated with DMPC/DHA in vivo. Furthermore, prolonged survival was obtained in the hepatic metastasis mouse models after the treatment with DMPC/DHA. Therapeutic effects of DMPC/DHA without any drugs on the hepatic metastasis were revealed on the basis of histological and biochemical analyses for the first time in vivo.
Asunto(s)
Antineoplásicos/administración & dosificación , Apoptosis/efectos de los fármacos , Carcinoma/tratamiento farmacológico , Carcinoma/secundario , Ácidos Docosahexaenoicos/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Carcinoma/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Dimiristoilfosfatidilcolina/química , Ácidos Docosahexaenoicos/química , Ácidos Docosahexaenoicos/uso terapéutico , Estabilidad de Medicamentos , Femenino , Células HCT116 , Humanos , Inyecciones Intravenosas , Liposomas , Hígado/efectos de los fármacos , Hígado/patología , Neoplasias Hepáticas/patología , Ratones , Ratones SCID , Tamaño de la Partícula , Vehículos Farmacéuticos/química , Distribución Aleatoria , Análisis de Supervivencia , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Accumulation of ß amyloid (Aß) peptides to nerve cells should be associated with the onset of Alzheimer's disease (AD). We prepared hybrid liposomes (HL) composed of 90 mol% phospholipids having various charged head groups (cationic L-α-dimyristoyltrimethyl ammonium propane (DMTAP), anionic L-α-dimyristoylphosphatidylserine (DMPS) or zwitterionic L-α-dimyristoylphosphatidylcholine (DMPC)) and 10 mol% polyoxyethylene(23) dodecyl ether (C(12)(EO)(23))), and investigated the inhibitory effects of HL on the accumulation of Aß(1-40) peptides into human neuroblastoma (SH-SY5Y) cells in vitro. It is noteworthy that remarkable inhibitory effects on the accumulation of Aß(1-40) peptides were observed for SH-SY5Y cells treated with anionic HL-DMPS, though the accumulation was not inhibited by cationic HL-DMTAP. On the other hand, the immediate fusion of HL-DMTAP into SH-SY5Y cells was confirmed using a confocal laser microscope. Interestingly, the specific interactions between anionic HL-DMPS and Aß(1-40) peptides were observed using the thioflavin T (ThT) assay. In addition, the cytotoxicity of Aß(1-42) peptides on the SH-SY5Y cells decreased after the treatment with HL-DMPS. These results suggest that anionic HL-DMPS could be used as a novel medicine for AD in the future.
