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具有 pH 响应性的金属有机框架封装的金纳米团簇,可控制释放,以增强乳腺癌的光动力疗法/化学疗法。

pH-Responsive metal-organic framework encapsulated gold nanoclusters with modulated release to enhance photodynamic therapy/chemotherapy in breast cancer.

机构信息

Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, College of Chemistry & Environmental Science, Hebei University, Baoding 071002, P. R. China.

Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices, & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, 315201, P. R. China.

出版信息

J Mater Chem B. 2020 Feb 26;8(8):1739-1747. doi: 10.1039/c9tb02621e.

DOI:10.1039/c9tb02621e
PMID:32030386
Abstract

Gold nanoclusters (AuNCs) with an ultra-small size, as new inorganic photosensitizers, have been shown to be promising in photodynamic therapy (PDT), but their application has been restricted due to short blood circulation. It is therefore important to develop stimuli-responsive AuNC-based nanoprobes to achieve highly efficient PDT. Here, metal-organic framework (MOF, ZIF-8) encapsulated AuNCs (AuNCs@MOF) were synthesized, and then they were loaded with doxorubicin (DOX) to obtain pH-responsive nanoprobes (AuNCs@MOF-DOX) with modulated release for enhanced PDT/chemotherapy. In an acidic tumor microenvironment, the structure of ZIF-8 collapsed, accelerating the release of the AuNCs and DOX in the tumor cells, and enhancing the performance of PDT/chemotherapy. Under irradiation with a 670 nm laser, a large amount of singlet oxygen was generated, and the release rate of DOX increased to 77.1% at a pH value of 5.5. By single PDT and single chemotherapy, the tumors were only partially inhibited, but they completely disappeared using the combination of PDT and chemotherapy. The prepared pH-responsive AuNCs@MOF-DOX nanoprobes with modulated release showed excellent PDT/chemotherapy performance, and will be important bi-functional nanoprobes for synergistic therapy.

摘要

金纳米团簇(AuNCs)具有超小尺寸,作为新型无机光敏剂,在光动力疗法(PDT)中表现出很大的应用潜力,但由于血液循环时间短,其应用受到限制。因此,开发响应型基于 AuNC 的纳米探针以实现高效 PDT 非常重要。在此,合成了金属有机骨架(MOF,ZIF-8)封装的 AuNCs(AuNCs@MOF),然后负载阿霉素(DOX)以获得具有调节释放的 pH 响应性纳米探针(AuNCs@MOF-DOX),用于增强 PDT/化疗。在酸性肿瘤微环境中,ZIF-8 的结构崩溃,加速了肿瘤细胞中 AuNCs 和 DOX 的释放,增强了 PDT/化疗的性能。在 670nm 激光照射下,大量单重态氧生成,在 pH 值为 5.5 时 DOX 的释放率增加到 77.1%。通过单一 PDT 和单一化疗,肿瘤仅部分受到抑制,但使用 PDT 和化疗联合治疗,肿瘤完全消失。所制备的具有调节释放的 pH 响应性 AuNCs@MOF-DOX 纳米探针表现出优异的 PDT/化疗性能,将成为协同治疗的重要双功能纳米探针。

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