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| 用于肿瘤光热治疗的血小板膜仿生纳米粒的体外初步研究 |
| 杨刚1,2,吴建明3,徐栋凯4,范清泽1,周佳涵4,万胜利1,4* |
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(1. 西南医科大学附属医院药学部, 泸州 646000;
2. 西南医科大学附属医院基建部, 泸州 646000;
3. 西南医科大学基础医学院, 泸州 646000;
4. 西南医科大学药学院, 泸州 646000
*通信作者) |
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| 摘要: |
| 目的 制备用于肿瘤光热治疗的载吲哚菁绿（ICG）血小板膜仿生纳米粒（ICG-PLP），并对其体外特性进行初步评价。方法 采用超声法制备ICG-PLP，并用激光粒度仪测定其粒径及zeta电位，用紫外分光光度法检测其包封率，在808 nm近红外光（2 W/cm2）照射下考察其光热性质，用SDS-PAGE观察血小板膜蛋白保留情况，用激光共聚焦显微镜考察制剂被小鼠巨噬细胞RAW264.7及人非小细胞肺癌细胞A549、小鼠黑色素瘤细胞B16-F10、小鼠乳腺癌细胞4T1摄取的情况，用MTT法检测ICG-PLP光毒性，通过考察溶血率及细胞相容性初步评价其安全性。在健康SD大鼠体内尾静脉注射给药后考察ICG、载ICG脂质体和ICG-PLP的体内循环时间。结果 成功制备了ICG-PLP，其平均包封率为（97.68±0.01）%，平均粒径为（109.77±0.76）nm，平均zeta电位为（－21.23±0.84）mV，多分散系数为0.22±0.01。ICG-PLP很好地保留了血小板膜上的蛋白质，并具有良好的光热性能。血小板膜能促进仿生纳米粒被A549、B16-F10、4T1等肿瘤细胞摄取，并减少巨噬细胞对仿生纳米粒的吞噬。ICG-PLP展示出良好的光热治疗效果，能杀伤肿瘤细胞，且有良好的安全性。静脉给药后，ICG-PLP能延长ICG在健康SD大鼠体内的滞留时间。结论 成功构建了ICG-PLP，其在药物靶向递送和肿瘤光热治疗方面具有很大的潜力。 |
| 关键词: 血小板膜 仿生纳米粒 光热疗法 肿瘤 |
| DOI：10.16781/j.CN31-2187/R.20230775 |
| 投稿时间：2023-12-28修订日期：2024-05-07 |
| 基金项目:四川省科技计划项目（2023NSFSC1862），泸州市人民政府与西南医科大学合作项目（2023LZXNYDJ009），西南医科大学基金（2019ZQN144，2023QN004），四川省大学生创新创业训练计划项目（S202310632132）． |
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| Platelet membrane biomimetic nanoparticles for tumor photothermal therapy: a preliminary in vitro study |
| YANG Gang1,2,WU Jianming3,XU Dongkai4,FAN Qingze1,ZHOU Jiahan4,WAN Shengli1,4* |
(1. Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China;
2. Department of Infrastructure, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China;
3. School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, Sichuan, China;
4. School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China
* Corresponding author) |
| Abstract: |
| Objective To prepare indocyanine green (ICG)-loaded platelet membrane biomimetic liposome (ICG-PLP) for tumor photothermal therapy, and to preliminarily evaluate its in vitro characteristics. Methods ICG-PLP was prepared by an ultrasound method, and its particle size and zeta potential were determined using a laser particle size analyzer. The encapsulation efficiency of ICG-PLP was detected by ultraviolet spectrophotometry. The photothermal properties of ICG-PLP were investigated under 808 nm near-infrared ray irradiation (2 W/cm2), and the retention of platelet membrane proteins was observed by sodium dodecylsulfate-polyacrylamide gel electrophoresis. The uptake of ICG-PLP by mouse macrophage RAW264.7, human non-small cell lung cancer cell A549, mouse melanoma cell B16-F10, and mouse breast cancer cell 4T1 was observed by a laser confocal microscope. Furthermore, the phototoxicity of ICG-PLP was detected by methyl thiazolyl tetrazolium assay, and the safety of ICG-PLP was preliminarily evaluated according to hemolysis rate and cytocompatibility. Besides, the in vivo retention time of ICG, ICG-loaded liposome and ICG-PLP in healthy SD rats was observed after tail vein injection. Results ICG-PLP was successfully prepared and its encapsulation efficiency, particle size, zeta potential, and the polydispersity index were (97.68±0.01)%, (109.77±0.76) nm, (－21.23±0.84) mV, and 0.22±0.01, respectively. ICG-PLP well retained the proteins on platelet membrane and showed good photothermal properties. Platelet membrane enhanced the uptake of biomimetic nanoparticles by tumor cells A549, B16-F10, and 4T1, and reduced the phagocytosis of biomimetic nanoparticles by macrophages. ICG-PLP exhibited a favorable photothermal therapy effect and could kill tumor cells. Additionally, ICG-PLP displayed a good safety. After intravenous administration, ICG-PLP prolonged the in vivo retention time of ICG in healthy SD rats. Conclusion ICG-PLP has been successfully constructed. It has a great potential in targeted drug delivery and tumor photothermal therapy. |
| Key words: platelet membrane biomimetic nanoparticles photothermal therapy neoplasms |
