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多功能金属有机框架纳米探针用于组织蛋白酶 B 激活的癌细胞成像和化学光动力治疗。

Multifunctional Metal-Organic Framework Nanoprobe for Cathepsin B-Activated Cancer Cell Imaging and Chemo-Photodynamic Therapy.

机构信息

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210023, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2017 Jan 25;9(3):2150-2158. doi: 10.1021/acsami.6b14446. Epub 2017 Jan 12.

DOI:10.1021/acsami.6b14446
PMID:28033467
Abstract

Integration of a photodynamic therapy platform with a drug-delivery system in a porous structure is an urgent challenge for enhanced anticancer therapy. Here, an amino-functionalized metal-organic framework (MOF), which is useful as efficient delivery vehicle for drugs and provides the -NH group for postsynthetic modification, is chosen and well-designed for cell imaging and chemo-photodynamic therapy. The multifunctional MOF nanoprobe was first assembled with camptothecine drug via noncovalent encapsulation and then bound with folic acid as the targeted element and chlorine e6 (Ce6)-labeled CaB substrate peptide as the recognition moiety and signal switch. The designed MOF probe can realize cathepsin B-activated cancer cell imaging and chemo-photodynamic dual-therapy combining Ce6 as the photosensitizer and the camptothecine drug. Compared with the individual treatment, the dual-functional nanoprobe presents an enhanced treatment efficiency in terms of the time of chemotherapy, laser power, and irradiation time of the photodynamic therapy, which has been confirmed in cancer cells and in vivo assays. This work presents a significant example of the MOF nanoprobe as an intracellular switch and shows great potential in cancer cell targeted imaging and multiple therapies.

摘要

将光动力治疗平台与多孔结构中的药物输送系统集成是增强抗癌治疗的迫切挑战。在这里,选择了一种氨基功能化的金属有机骨架(MOF),它可用作药物的有效输送载体,并提供用于后期合成修饰的 -NH 基团。该 MOF 被设计用于细胞成像和化学-光动力治疗。多功能 MOF 纳米探针首先通过非共价包封与喜树碱药物组装,然后与叶酸结合作为靶向元素,氯 e6(Ce6)标记的 CaB 底物肽作为识别部分和信号开关。设计的 MOF 探针可以实现组织蛋白酶 B 激活的癌细胞成像和化学-光动力双重治疗,Ce6 作为光敏剂和喜树碱药物。与单独治疗相比,双功能纳米探针在化疗时间、激光功率和光动力治疗的照射时间方面表现出更高的治疗效率,这在癌细胞和体内实验中得到了证实。这项工作为 MOF 纳米探针作为细胞内开关提供了一个重要的范例,并显示出在癌细胞靶向成像和多种治疗方面的巨大潜力。

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