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Cathepsin B 响应性肽-卟啉缀合物组装引发原位自聚集用于癌症声热治疗。

Cathepsin B Responsive Peptide-Purpurin Conjugates Assembly-Initiated in Situ Self-Aggregation for Cancer Sonotheranostics.

机构信息

State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, School of Public Health, Xiamen University, Xiamen 361102, China.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.

出版信息

Nano Lett. 2024 Jan 24;24(3):950-957. doi: 10.1021/acs.nanolett.3c04371. Epub 2024 Jan 10.

Abstract

Sonodynamic therapy (SDT) was hampered by the sonosensitizers with low bioavailability, tumor accumulation, and therapeutic efficiency. In situ responsive sonosensitizer self-assembly strategy may provide a promising route for cancer sonotheranositics. Herein, an intelligent sonotheranostic peptide-purpurin conjugate (P18-P) is developed that can self-assemble into supramolecular structures via self-aggregation triggered by rich enzyme cathepsin B (CTSB). After intravenous injection, the versatile probe could achieve deep tissue penetration because of the penetration sequence of P18-P. More importantly, CTSB-triggered self-assembly strongly prolonged retention time, amplified photoacoustic imaging signal for sensitive CTSB detection, and boosted reactive oxygen species for advanced SDT, evoking specific CTSB responsive sonotheranostics. This peptide-purpurin conjugate may serve as an efficient sonotheranostic platform for the early diagnosis of CTSB activity and effective cancer therapy.

摘要

声动力学疗法(SDT)受到生物利用度低、肿瘤积累和治疗效率低的声敏剂的阻碍。原位响应声敏剂自组装策略可能为癌症声热疗法提供一条有前途的途径。本文开发了一种智能声热疗肽-卟啉偶联物(P18-P),它可以通过富含组织蛋白酶 B(CTSB)的自聚集触发自组装成超分子结构。静脉注射后,由于 P18-P 的渗透序列,多功能探针可以实现深层组织穿透。更重要的是,CTSB 触发的自组装强烈延长了保留时间,放大了光声成像信号,以敏感检测 CTSB,并增强了活性氧以进行高级 SDT,引发特定的 CTSB 响应声热疗。这种肽-卟啉偶联物可以作为一种有效的声热诊断平台,用于早期诊断 CTSB 活性和有效治疗癌症。

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