| 黄菊,李攀,王志刚,韩晓霞,刘逢秋.载血卟啉单甲醚高分子纳米粒用于光声显像引导下声动力治疗:实验研究[J].中国医学影像技术,2019,35(1):30~35 |
| 载血卟啉单甲醚高分子纳米粒用于光声显像引导下声动力治疗:实验研究 |
| Experimental study of hematoporphyrinmonomethyl ether based PLGA nanoparticles for photoacoustic imaging-guided sonodynamic therapy |
| 投稿时间：2018-04-18 修订日期：2018-10-09 |
| DOI：10.13929/j.1003-3289.201804096 |
| 中文关键词: 血卟啉单甲醚 光声成像 声动力治疗 纳米医学 |
| 英文关键词:hematoporphyrinmonomethyl ether photoacoustic imaging sonodynamic therapy nanomedicine |
| 基金项目:国家自然科学基金（81371578、81771847、31630026、81630047、81771845）。 |
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| 中文摘要: |
| 目的 制备一种载血卟啉单甲醚（HMME）的多功能分子探针，评估其体外光声成像及声动力治疗（SDT）效果。方法 采用双乳化法制备载HMME的聚乳酸-乙醇酸（PLGA）纳米粒（HMME@PLGA），观察纳米粒的基本表征和体外增强光声显像情况，通过流式细胞仪检测人乳腺癌MDA-MB-231细胞与HMME@PLGA共孵育后在超声辐照下产生活性氧的能力，并在细胞水平验证其SDT效果。结果 所制备的HMME@PLGA纳米粒大小均一，形态规则，平均粒径为（333.67±17.50）nm，表面电位为（-10.57±1.98）mV，包封率为75.62%，载药量为2.90%，浓度为1 mg/ml的纳米粒与人乳腺癌MDA-MB-231细胞共孵育24 h的细胞存活率为87.21%。随浓度增加，纳米粒光声信号逐渐增强。经超声辐照，HMME@PLGA纳米粒能使人乳腺癌MDA-MB-231细胞产生大量活性氧，并产生明显细胞毒性作用，使细胞大量死亡，Calcein-AM/PI染色呈红色荧光；通过吖啶橙染色观测到细胞溶酶体结构消失。结论 本研究成功制备了包裹HMME的高分子纳米粒，可实现体外光声成像引导下的SDT。 |
| 英文摘要: |
| Objective To prepare hematoporphyrinmonomethyl ether (HMME) based poly (lactic-co-glycolic acid) (PLGA) nanoparticles, and to investigate their enhancement effect on photoacoustic (PA) imaging and sonodynamic therapy (SDT) efficacy in vitro. Methods HMME-based PLGA (HMME@PLGA) nanoparticles were synthesized using a facile double emulsion strategy. The characteristics and enhanced PA imaging capability were observed in vitro. Upon ultrasound irradiation, the reactive oxygen species (ROS) generated with MDA-MB-231 cells up-taken HMME@PLGA was investigated using flow cytometry. SDT efficacy on cellular level was further investigated. Results The fabricated HMME@PLGA nanoparticles were demonstrated with homogenized size and distribution, and the average diameter was (333.67±17.50)nm. The Zeta potential was (-10.57±1.98)mV. The encapsulation efficiency of HMME in HMME@PLGA was 75.62%, and the drug loading was 2.90%. When incubation with HMME@PLGA nanoparticles (1 mg/ml) for 24 h, the viability of MDA-MB-231 cells was 87.21%. PA signal intensities increased with the increase of HMME@PLGA concentration in vitro. Upon ultrasound irradiation, ROS was produced in MDA-MB-231 cells with the assistance of HMME@PLGA nanoparticles, further leading to cytotoxic effects and cellular death which showed obvious red fluorescence stained with Calcein-AM/PI. Meanwhile, the lysosomes structures of the dead cells disappeared when stained by acridine orange. Conclusion HMME@PLGA nanoparticles are successfully fabricated and can achieve PA imaging-guided SDT. |
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