宗玲, 袁安然, 朱耀, 顾云双, 戈延茹, 沈松. 负载吲哚菁绿和多柔比星的温敏胶束在MCF-7肿瘤细胞治疗中的联合应用J. 药学学报, 2018,53(7): 1169-1176. doi: 10.16438/j.0513-4870.2018-0291
引用本文: 宗玲, 袁安然, 朱耀, 顾云双, 戈延茹, 沈松. 负载吲哚菁绿和多柔比星的温敏胶束在MCF-7肿瘤细胞治疗中的联合应用J. 药学学报, 2018,53(7): 1169-1176. doi: 10.16438/j.0513-4870.2018-0291
ZONG Ling, YUAN An-ran, ZHU Yao, GU Yun-shuang, GE Yan-ru, SHEN Song. Preparation of thermoresponsive micelles loaded with indocyanine green and doxorubicin for combined therapy in MCF-7 cellsJ. Acta Pharmaceutica Sinica, 2018,53(7): 1169-1176. doi: 10.16438/j.0513-4870.2018-0291
Citation: ZONG Ling, YUAN An-ran, ZHU Yao, GU Yun-shuang, GE Yan-ru, SHEN Song. Preparation of thermoresponsive micelles loaded with indocyanine green and doxorubicin for combined therapy in MCF-7 cellsJ. Acta Pharmaceutica Sinica, 2018,53(7): 1169-1176. doi: 10.16438/j.0513-4870.2018-0291

负载吲哚菁绿和多柔比星的温敏胶束在MCF-7肿瘤细胞治疗中的联合应用

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

  • 摘要: 本文利用无规共聚法制备温敏胶束,通过物理吸附将光敏剂吲哚菁绿(indocyanine,ICG)负载在胶束上,在近红外光照射后,将光能转化为热能,使温度升高,达到相变温度后发生解聚,从而实现特异性治疗。采用透射电镜、核磁共振波谱仪和傅立叶红外光谱仪等手段对胶束进行表征;对多柔比星(doxorubicin,DOX)进行负载,考察所制备载体的临界胶束浓度(critical micelle concentration,CMC)、高临界溶解温度、光热性能及光控释药结果。此外,对空白载体及载药载体的细胞摄取、体外毒性及光热、光热-化疗联合治疗的效果进行了研究。结果表明,所制备的胶束p(AAm-co-AN)-g-PEG (PAAP)形状均一,呈类球形,粒径约45 nm,相变温度为43℃左右,CMC约为24 μg·mL-1;负载ICG及DOX后(DOX-ICG-PAAP),胶束粒径增加至88 nm,且光热效果明显,给予近红外光(808 nm,2 W·cm-2,2 min·h-1)照射后,5 h药物累计释放率可增加到59.4%(pH 5.0);细胞实验结果显示,空白载体ICG-PAAP无显著毒性,可通过溶酶体途径摄取,结合化疗后,当DOX质量浓度为20 μg·mL-1时,照射3 min可杀伤70%以上的细胞。以上结果表明,所制备的胶束具有温敏性且毒性较低,在近红外光照射下,可促进药物加快释放从而实现光热化疗联合抗肿瘤的效果。

     

    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.

     

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