亚细胞器靶向的碳量子点在双光子诊疗中的应用研究

Two-photon excitation phototheranostics combines the diagnosis and subsequent treatment of a disease using a single agent system; as a novel category of clinical solution, it has been demonstrated potentials of early detection and rapid treatment of diseases such as cancer. Nevertheless, as the core element of phototheranostics, the current photosensitizers have in general poor photostability and water dispersibility, low two-photon absorption cross-section, low reactive oxygen species quantum yield and non-subcellular targeting which hamper their clinical applications. This project will focus on the synthesis of heteroatom-doped biocompatible carbon dots (CDs) which have large two-photon absorption cross-section, high reactive oxygen species quantum yield, long wavelength emissive and have the ability to target subcellular organelles. The impacts of microstructure, doping, surface modification on the photochemical, photophysical and biophysical properties of CDs will be studied systematically. The mechanisms of photoluminescence and the decay of excited state of CDs will be investigated. The corresponding characteristics of CDs, such as two-photon absorption cross-section, emission wavelength, reactive oxygen species and the subcellular targeting capability will be related. Based on that, novel CDs-based photosensitizers will be developed and applied in two-photon excitation phototheranostics of cancer. The expected results of this proposal will provide a new approach for the preparation of high-efficiency photosensitizers.

双光子诊疗作为一种新型的临床治疗手段，具有精准定位和光控治疗的优点，为癌症等重大疾病的精确诊断和高效治疗提供了有效的手段。然而其核心元素光敏剂大多存在光稳定性差、水溶性差、双光子吸收截面小、发光波长短、活性氧量子产率低、不具备亚细胞器靶向能力等诸多难题，显著影响其优势的发挥。本项目以恶性肿瘤的高效双光子诊疗为目标，拟从纳米科学技术和双光子诊疗的基本原理出发，发展具有大双光子吸收截面、高活性氧量子效率、长波长发光，且具有亚细胞器靶向功能的低毒性碳量子点光敏剂，研究碳量子点的纳米结构、掺杂、表面修饰对其光化学光物理性质、生物物理性质的影响，阐明其发光机理和激发态失活过程，揭示影响碳量子点的双光子吸收截面、发光波长、活性氧量子产率及亚细胞器靶向能力的关键因素。在此基础上，构筑亚细胞器靶向的碳量子点光敏剂，最终用于恶性肿瘤的高效双光子诊疗。预期成果将为发展新型临床使用的高效光敏剂提供新的技术基础。

光诊疗作为一种新型的临床快速诊断同时高效治疗癌症等重大疾病的新技术，它具有精准定位和光控治疗的优点。然而临床上所用的光敏剂面临着激发/发光波长短，水溶性差，活性氧量子产率低、肿瘤靶向性较弱等缺点，严重影响了其光诊疗的性能。本项目在前期研究的基础上，以恶性肿瘤的高效光诊疗为目标牵引，从纳米科学技术和光诊疗的基本原理出发，设计并合成了一系列双光子激发荧光性质、不同发光波长、具有较高活性氧产率或光热转换效率、具有溶酶体或线粒体靶向功能的碳点，阐明了影响碳点光化学光物理性质及其亚细胞器靶向能力的关键因素；设计合成了若干有机光诊疗，通过精准的分子设计，实现了有机光诊疗剂荧光、活性氧产率和光热转换效率之间的调控。将制备碳点和有机光诊疗应用于肿瘤细胞和肿瘤组织的光诊疗，并系统评估了其生物安全性。本项目的研究成果为高性能光敏剂的设计和制备提供理论依据和重要的技术支撑。

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