Preparation of thermoresponsive micelles loaded with indocyanine green and doxorubicin for combined therapy in MCF-7 cells / 药学学报

ABSTRACT

In this study, the thermoresponsive micelles were synthesized with random copolymerization method and the photosensitizer indocyanine green (ICG) was loaded on micelles through the physical adsorption. The light energy was converted into heat energy to increase the temperature after irradiation with near-infrared light. When the phase transition temperature was reached, the micelle was disassembled and the targeted therapy was achieved. The nanoparticles were characterized with a transmission electron microscopy, Fourier transform infrared spectrometer, nuclear magnetic resonance spectrometer and other characterization were used to investigate. The critical micelle concentration (CMC), upper critical solution temperature, the photothermal properties of the carrier and the release of drug triggered by light were investigated after the doxorubicin (DOX) loaded. The carrier was evaluated for toxicity, cellular uptake, the effect of photothermal, the combination of photothermal and chemotherapy; the p(AAm-co-AN)-g-PEG (PAAP) was spherical in shape with a particle size of about 45 nm and a phase transition temperature was about 43℃. The critical micelle concentration was 24 μg·mL-1. The particle size increased to 88 nm after loaded with ICG and DOX which the photothermal effect was obvious. The cumulative release of the drug under the irradiation of near-infrared light (808 nm, 2 W·cm-2, 2 min·h-1) was increased to 59.4% (pH 5.0) after 5 h. The results of the cell experiment indicated that ICG-PAAP was almost non-toxic and uptaken by the lysosomal pathway. The cell killing effect was stronger with combination of chemotherapy (DOX as 20 μg·mL-1) with more than 70% of the cells killed. The results showed that the prepared micelle with low toxicity was thermoresponsive and could be used in combined therapy of tumor under the irradiation of near-infrared light.