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光触发仿生纳米红细胞用于恶性黑色素瘤肺转移的肿瘤靶向联合治疗。

Light-Triggered Biomimetic Nanoerythrocyte for Tumor-Targeted Lung Metastatic Combination Therapy of Malignant Melanoma.

机构信息

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, 510632, China.

The School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA 6009, Australia.

出版信息

Small. 2018 Sep;14(38):e1801754. doi: 10.1002/smll.201801754. Epub 2018 Aug 23.

Abstract

Red blood cell (RBC) membrane-cloaked nanoparticles, reserving the intact cell membrane structure and membrane protein, can gain excellent cell-specific functions such as long blood circulation and immune escape, providing a promising therapy nanoplatform for drug delivery. Herein, a novel RBC membrane biomimetic combination therapeutic system with tumor targeting ability is constructed by embedding bovine serum albumin (BSA) encapsulated with 1,2-diaminocyclohexane-platinum (II) (DACHPt) and indocyanine green (ICG) in the targeting peptide-modified erythrocyte membrane (R-RBC@BPtI) for enhancing tumor internalization and synergetic chemophototherapy. R-RBC@BPtI displays excellent stability and high encapsulation efficiency with multiple cores enveloped in the membrane. Benefited from the stealth functionality and targeting modification of erythrocyte membranes, R-RBC@BPtI can significantly promote tumor targeting and cellular uptake. Under the near-infrared laser stimuli, R-RBC@BPtI presents remarkable instability by singlet oxygen and heat-mediated cleavage so as to trigger effective drug release, thereby achieving deep penetration and accumulation of DACHPt and ROS in the tumor site. Consequently, R-RBC@BPtI with tumor-specific targeting ability accomplishes remarkable ablation of tumors and suppressed lung metastasis in vivo by photothermal and chemotherapy combined ablation under phototriggering. This research provides a novel strategy of targeted biomimetic nanoplatforms for combined cancer chemotherapy-phototherapy.

摘要

红细胞膜伪装纳米颗粒保留了完整的细胞膜结构和膜蛋白,可以获得优异的细胞特异性功能,如长血液循环和免疫逃逸,为药物输送提供了一种有前途的治疗纳米平台。在此,通过将牛血清白蛋白(BSA)包裹的 1,2-二氨基环己烷-铂(II)(DACHPt)和吲哚菁绿(ICG)嵌入靶向肽修饰的红细胞膜(R-RBC@BPtI)中,构建了一种具有肿瘤靶向能力的新型红细胞膜仿生组合治疗系统,以增强肿瘤内化和协同化学-光疗。R-RBC@BPtI 表现出优异的稳定性和高包封效率,多个核被包裹在膜中。受益于红细胞膜的隐身功能和靶向修饰,R-RBC@BPtI 可以显著促进肿瘤靶向和细胞摄取。在近红外激光刺激下,R-RBC@BPtI 通过单线态氧和热介导的裂解表现出显著的不稳定性,从而触发有效药物释放,从而实现 DACHPt 和 ROS 在肿瘤部位的深度渗透和积累。因此,具有肿瘤特异性靶向能力的 R-RBC@BPtI 通过光热和化学联合消融在光触发下实现了显著的肿瘤消融和体内肺转移抑制。这项研究为联合癌症化学-光疗提供了一种新的靶向仿生纳米平台策略。

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