RESUMEN
The targeted drug delivery with the help of nanocarriers and the controlled drug release at the lesion sites are the most effective ways to enhance therapeutic efficacy and reduce side effects. Here, we built a light sensitive liposome (Her2-I&D-LSL) which was formed by a special phospholipid (PLsPC) and a hydrophobically modified photosensitizer (ICG-ODA). DOX was employed as the therapeutic drug, encapsulating in the internal phase of the liposome whose surface was modified by Her2 antibodies for recognizing tumor cells with high Her2 receptor expression. Mediated by NIR light, Her2-I&D-LSL was proved to generate sufficient ROS to realize PDT, which then triggered the release of DOX for combined chemotherapy. The ROS generation and DOX release were verified to be strictly controlled by NIR light and the proportion of ICG-ODA. Thanks to the mediation of Her2 receptor, the specific DOX release and the combination of PDT-chemotherapy triggered by NIR light, Her2-I&D-LSL showed a significant accumulation in MCF7 and SKOV3 tumors, thus leading to the strongest tumor growth inhibition effect compared to PDT alone (I-LSL) or chemotherapy alone (D-LSL). Her2-I&D-LSL also possessed a great biocompatibility due to the targeted treatment, holding promise for future cancer therapy in clinic.
Asunto(s)
Antibióticos Antineoplásicos/metabolismo , Doxorrubicina/metabolismo , Liberación de Fármacos/fisiología , Estimulación Luminosa/métodos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/metabolismo , Células A549 , Animales , Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Humanos , Liposomas , Células MCF-7 , Masculino , Ratones , Ratones Desnudos , Fármacos Fotosensibilizantes/administración & dosificaciónRESUMEN
AIMS: To prepare 5-fluorouracil (5-Fu) nanoparticles with higher encapsulation efficiency and drug loading, and then investigate interaction with the SGC-7901 gastric cancer cell line. MATERIALS AND METHODS: Prescription was optimized by orthogonal experiments, the encapsulation efficiency and loading capacity were tested by high- performance liquid chromatography, and inhibition of proliferation by 5-Fu nanoparticles and 5-Fu given to cells for 24, 48 and 72 hours was investigated by methyl thiazolyl tetrazolium assay (MTT). In addition, 5-Fu nanoparticles were labeled by fluorescein isothiocyanate (FITC), and absorption into cells was tested by flow cytometry. RESULTS: The optimal conditions for preparation were concentrations of 5-Fu of 5mg/ml, of CaCl2 of 60 mg/ml and of chitosan of 2 mg/ml. With a stirring speed of 1200rpm, encapsulation efficiency of 5-Fu nanoparticles was 55.4±1.10% and loading capacity was 4.22±0.14%; gastric cancer cells were significantly inhibited by 5-Fu nanoparticles in a time and concentration dependent manner, and compared to 5-Fu with slower drug release, in a certain concentration range, inhibition with 5-Fu nanoparticles was stronger. 5-Fu nanoparticles were absorbed by the cells in line with the concentration. CONCLUSIONS: 5-Fu nanoparticles can inhibit growth of gastric cancer cells in vitro to a greater extent than with 5-Fu with good adsorption characteristics, supporting feasibility as a carrier.