李士壮, 阚玉萍, 陈铭, 苏慧, 阎雪莹. 肺癌细胞膜涂层的DOX和IR820的光热敏感型仿生脂质体用于癌症的化学-光热-光动力治疗J. 药学学报, 2024, 59(5): 1430-1440. DOI: 10.16438/j.0513-4870.2023-1087
引用本文: 李士壮, 阚玉萍, 陈铭, 苏慧, 阎雪莹. 肺癌细胞膜涂层的DOX和IR820的光热敏感型仿生脂质体用于癌症的化学-光热-光动力治疗J. 药学学报, 2024, 59(5): 1430-1440. DOI: 10.16438/j.0513-4870.2023-1087
LI Shi-zhuang, KAN Yu-ping, CHEN Ming, SU Hui, YAN Xue-ying. Photothermal-sensitive biomimetic liposomes coated with DOX and IR820 for chemo-photothermal-photodynamic therapy of cancer in lung cancer cellsJ. Acta Pharmaceutica Sinica, 2024, 59(5): 1430-1440. DOI: 10.16438/j.0513-4870.2023-1087
Citation: LI Shi-zhuang, KAN Yu-ping, CHEN Ming, SU Hui, YAN Xue-ying. Photothermal-sensitive biomimetic liposomes coated with DOX and IR820 for chemo-photothermal-photodynamic therapy of cancer in lung cancer cellsJ. Acta Pharmaceutica Sinica, 2024, 59(5): 1430-1440. DOI: 10.16438/j.0513-4870.2023-1087

肺癌细胞膜涂层的DOX和IR820的光热敏感型仿生脂质体用于癌症的化学-光热-光动力治疗

Photothermal-sensitive biomimetic liposomes coated with DOX and IR820 for chemo-photothermal-photodynamic therapy of cancer in lung cancer cells

  • 摘要: 本研究构建以多柔比星(doxorubicin, DOX) 为模型药物、新吲哚菁绿(IR820) 为光敏剂、温度敏感脂质体(temperature sensitive liposomes, TSL) 为载体, H460-NCI人大细胞肺癌细胞膜涂层的光热敏感脂质体(DOX-IR820-TSL@CCM), 用于化学-光热治疗-光动力治疗的多途径高效肿瘤靶向作用。采用逆向蒸发法制备DOX-IR820-TSL, 通过裂解、破碎、离心等方法制备癌细胞膜(cancer cell membrane, CCM), 采用纳米膜挤压法制备DOX-IR820-TSL@CCM; 并对上述脂质体进行表征。最终确定DOX-IR820-TSL的载药条件如下: 有机相与水相比例为4.02, 二棕榈酰磷脂酰胆碱(dipalmitoyl-sn-glycero-3-phosphocholine, DPPC) 用量为10.04 mg, 药脂比为0.12, DOX-IR820-TSL显著相变温度(Tm)为43.05 ℃, DOX-IR820-TSL@CCM平均粒径为153.4 nm, PDI为0.279, zeta电位为-26.2 mV。透射电子显微镜图像在图中显示出均匀的球形结构和半透明膜层。在近红外光照射下, 药物释放率达到了63.98%, 具有可调节的光热转化能力和产生活性氧的能力。通过SDS-PAGE电泳、Western blot、细胞毒性实验和细胞摄取实验, 证明了细胞膜涂层的设计能够很好地保留CD47、N-cadherin、CD44、CD326等相关功能蛋白, 使DOX-IR820-TSL@CCM具备良好的免疫逃逸、同源黏附和同源靶向作用。本文制备了具有伪装特性和肿瘤靶向性的DOX-IR820-TSL@CCM, 可作为一种协同治疗诊断平台用于未来的肺癌治疗。所有动物研究方案均已通过黑龙江中医药大学动物伦理委员会批准(编号为: 2022121011)。

     

    Abstract: In this study, doxorubicin (DOX) was used as the model drug, new indocyanine green (IR820) as the photosensitizer, and temperature sensitive liposomes (TSL) as the carrier. H460-NCI photoheat-sensitive liposomes coated with cell membrane of human cell lung cancer (DOX-IR820-TSL@CCM) for highly effective multi-pathway tumor targeting in chemical-photothermal therapy and photodynamic therapy. DOX-IR820-TSL was prepared by reverse evaporation, cancer cell membrane (CCM) was prepared by lysis, crushing and centrifugation, and DOX-IR820-TSL@CCM was prepared by nanomembrane extrusion. The drug-loading conditions of DOX-IR820-TSL were finally determined: the ratio of organic phase to aqueous phase was 4.02, the dosage of dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was 10.04 mg, and the lipid ratio was 0.12, and the significant phase transition temperature (Tm) of DOX-IR820-TSL was 43.05 ℃. The average particle size of DOX-IR820-TSL@CCM was 153.4 nm, the PDI was 0.279, and the zeta potential was -26.2 mV. The transmission electron microscope (TEM) image shows a homogeneous spherical structure and a translucent film layer. Under near-infrared irradiation, the drug release rate reaches 63.98%, which has adjustable photothermal conversion capacity and the ability to generate reactive oxygen species. Through SDS-PAGE electrophoresis, Western blot, cytotoxicity experiments and cell uptake experiments, it was proved that the design of cell membrane coating can well retain CD47, N-cadherin, CD44, CD326 and other related functional proteins, so that DOX-IR820-TSL@CCM has good immune evasion, homologous adhesion and homologous targeting. In this paper, DOX-IR820-TSL@CCM with camouflage properties and tumor targeting properties were successfully prepared, which can be used as a promising synergistic therapeutic diagnostic platform for future lung cancer treatment. All animal research programs have been approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine (number: 2022121011).

     

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