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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release
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Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

机译：用于肿瘤靶向多峰成像和治疗性药物释放的集成纳米技术平台

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A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.
机译：在癌症中靶向分子成像和药物递送的主要挑战是建立配体导向货物与触发释放系统的功能组合。在这里，我们开发了一种基于水凝胶的纳米技术平台，该平台将肿瘤靶向，光子至热转换以及触发的药物传递整合到单个纳米结构中，以实现多模式成像和治疗性药物的受控释放。在概念验证实验中，我们展示了噬菌体颗粒，热敏脂质体或介孔二氧化硅纳米颗粒（可自组装成水凝胶用于肿瘤靶向药物输送）的各种基于配体肽的应用。因为纳米粒子密集地堆积在纳米载体中，所以它们的表面等离子体共振转移到近红外，从而实现了激光介导的货物释放的光热机制。我们在乳腺癌和前列腺癌的临床前小鼠模型中展示了非侵入性成像和靶向药物递送。最后，我们应用数学模型来预测和确认肿瘤靶向和药物递送。这些结果是朝着具有广泛临床应用潜能的纳米技术平台的设计和初始转换迈出的有意义的一步。

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