<br>基于光诱导电子转移的谷胱甘肽传感治疗诊断纳米前药，具有自我跟踪和实时药物释放监测功能，用于癌症治疗,ACS Applied Materials & Interfaces

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基于光诱导电子转移的谷胱甘肽传感治疗诊断纳米前药，具有自我跟踪和实时药物释放监测功能，用于癌症治疗
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2024-02-01 , DOI: 10.1021/acsami.3c16585
Safiya Nisar ₁ , Elisabeth Starosta ₁ , Mouhmad Elayyan ₁ , Amrit Regmi ₁ , Binglin Sui ₁

Affiliation

纳米医学的快速发展极大地推进了癌症治疗的精准治疗。新兴的治疗诊断纳米前药优于传统化疗，可以有效实现化疗药物固有的自我跟踪、靶向药物递送、刺激触发药物释放和降低全身毒性。然而，迄今为止，具有实时药物释放监测的治疗诊断纳米前药仍然很少。在这项工作中，我们开发了一种新型谷胱甘肽响应性治疗诊断纳米前药，其载药量高达59.4 wt%，平均纳米尺寸为46 nm，由抗癌药物紫杉醇和具有高荧光量子产率的荧光成像探针组成，它们通过基于二硫键的谷胱甘肽敏感的自毁连接体连接。荧光团的强荧光发射可实现有效的自跟踪和灵敏的荧光“开-关”谷胱甘肽传感。当癌细胞中遇到高水平的谷胱甘肽时，二硫键被裂解，所得的连接基半部以相同的速度自发塌陷成环状小分子，导致治疗药物和荧光关闭成像探针同时释放。因此，通过纳米前药的荧光变化有效地监测药物释放过程。纳米前药对多种癌细胞具有较高的细胞毒性，特别是对于A549和HEK-293细胞，纳米前药比游离紫杉醇产生更好的治疗效果。我们的工作展示了一种用于精确癌症治疗的智能治疗诊断纳米前药的新模式。

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Photoinduced Electron Transfer-Based Glutathione-Sensing Theranostic Nanoprodrug with Self-Tracking and Real-Time Drug Release Monitoring for Cancer Treatment

The rapid development of nanomedicine has considerably advanced precision therapy for cancer treatment. Superior to traditional chemotherapy, emerging theranostic nanoprodrugs can effectively realize inherent self-tracking, targeted drug delivery, stimuli-triggered drug release, and reduced systemic toxicity of chemotherapeutic drugs. However, theranostic nanoprodrugs with real-time drug release monitoring have remained rare so far. In this work, we developed a new glutathione-responsive theranostic nanoprodrug with a high drug-loading content of 59.4 wt % and an average nanoscale size of 46 nm, consisting of the anticancer drug paclitaxel and a fluorescent imaging probe with a high fluorescence quantum yield, which are linked by a disulfide-based glutathione-sensitive self-immolating linker. The strong fluorescence emission of the fluorophore enables efficacious self-tracking and sensitive fluorescence “ON-OFF” glutathione sensing. Upon encountering high-level glutathione in cancer cells, the disulfide bond is cleaved, and the resulting linker halves spontaneously collapse into cyclic small molecules at the same pace, leading to the simultaneous release of the therapeutic drug and the fluorescence-OFF imaging probe. Thereby, the drug release process is efficiently monitored by the fluorescence change in the nanoprodrug. The nanoprodrugs exerted high cytotoxicity toward various cancer cells, especially for A549 and HEK-293 cells, in which the nanoprodrugs generated better therapeutic effects than free paclitaxel. Our work demonstrated a new modality of smart theranostic nanoprodrugs for precise cancer therapy.

更新日期：2024-02-01

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