RESUMEN
The integration of various therapy strategies into a single nanoplatform for synergistic cancer treatment has presented a great prospect. Herein, docetaxel (DTX)-loaded poly lactic-co-glycolic acid (PLGA)-coated polydopamine modified with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) was synthesized for chemo-photothermal synergistic therapy against cancer. Firstly, the DTX-loaded PLGA NPs were prepared by a facile and robust nanoprecipitation method. Then, they were coated with dopamine to achieve the photothermal effects and to be further modified with TPGS, which can inhibit the P-glycoprotein-mediated multidrug resistance (MDR). The near-infrared (NIR) laser irradiation triggered DTX release from DTX-loaded PLGA NPs@PDA-TPGS, and then the chemo-photothermal therapy effect could be enhanced. The in vitro experimental results illustrated that DTX-loaded PLGA NPs@PDA-TPGS exhibits excellent photothermal conservation properties and remarkable cell-killing efficiency. In vivo antitumor studies further confirmed that DTX-loaded PLGA NPs@PDA-TPGS could present an outstanding synergistic antitumor efficacy compared with any monotherapy. This work exhibits a novel nanoplatform, which could not only load chemotherapy drugs efficiently, but could also improve the therapeutic effect of chemotherapy drugs by overcoming MDR and light-mediated photothermal cancer therapy.
Asunto(s)
Antineoplásicos/administración & dosificación , Resistencia a Antineoplásicos , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Nanopartículas/química , Fototerapia/métodos , Taxoides/administración & dosificación , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Docetaxel , Dopamina/química , Liberación de Fármacos , Femenino , Humanos , Ácido Láctico/química , Células MCF-7 , Neoplasias Mamarias Experimentales/terapia , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/uso terapéutico , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Taxoides/farmacocinética , Taxoides/uso terapéutico , Vitamina E/químicaRESUMEN
In this study, we introduced a targeting polymer poly(ethylene glycol)-folic acid (PEG-FA) on the surface of polydopamine (PDA)-modified mesoporous silica nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA-PEG-FA, which were employed as a drug delivery system loaded with doxorubicin (DOX) as a model drug for cervical cancer therapy. The chemical structure and properties of these NPs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, N2 adsorption/desorption, dynamic light scattering-autosizer, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The pH-sensitive PDA coating served as a gatekeeper. The in vitro drug release experiments showed pH-dependent and sustained drug release profiles that could enhance the therapeutic anticancer effect and minimize potential damage to normal cells due to the acidic microenvironment of the tumor. These MSNs@PDA-PEG-FA achieved significantly high targeting efficiency, which was demonstrated by the in vitro cellular uptake and cellular targeting assay. Compared with that of free DOX and DOX-loaded NPs without the folic targeting ligand, the FA-targeted NPs exhibited higher antitumor efficacy in vivo, implying that they are a highly promising potential carrier for cancer treatments.