具有NIR热刺激响应和射线敏感的纳米诊疗剂治疗黑色素瘤的机制研究

葡萄膜黑色素瘤是成人最常见的原发性眼内恶性肿瘤，中等大小的肿瘤治疗上首选局部放疗，但存在放射剂量大、并发症多等问题。放疗联合热疗是提高其治疗效率的有效策略之一，但存在射线剂量高和光热转化效率低的问题。我们前期研究发现，石墨烯量子点（GQDs）具有一定的放射增敏作用和近红外响应性，但在体液环境下GQDs不稳定、血液滞留性差和光热转化效率低的问题限制其作为增敏剂应用。本研究通过在GQDs表面化学修饰纳米金掺杂的聚多巴胺，改进在生理环境下的稳定性和光热转化效率，并通过连接核酸适配体AS1411构建具有肿瘤靶向作用的纳米增敏剂，进一步从分子、细胞和动物水平评价纳米增敏剂生物安全性、靶向效率、细胞摄取机制、药代动力学和放/热疗作用机制。本项目通过开发一种安全高效的放/热疗纳米增敏剂，实现肿瘤无创、精准、安全和高效治疗，推动放/热联合疗法在肿瘤临床治疗中的应用。

Uveal melanoma is the most common primary intraocular malignant tumor in adults, and local radiotherapy is the first choice for the treatment of medium-sized tumors, but there are many problems such as high irradiation dose and severe complications. Radiotherapy combined with thermal therapy is one of the effective strategies to improve the efficiency of its treatment. While, there are problems of high radiation dose and low photothermal conversion efficiency. Our previous studies have found that graphene quantum dots (GQDs) have a certain radiosensitizing effect and near-infrared thermal response. However, due to unstability, poor blood retention and low photothermal conversion efficiency in body fluid environment, GQDs are limited to be used as nanosensitizers. In this study, Polydopamine doped with gold nanoparticles will be chemically modified on the surface of GQDs to improve the stability and photothermal conversion efficiency in the physiological environment. Then, linking with aptamer AS1411, a tumor targeting nano-sensitizer (GQDs@PDA/Au-Apt) will be developed. This study will also evaluate the biosafety, cellular uptake, pharmacokinetics, and therapeutic mechanism at the moelular, cellular, and animal levels. This project will develop a safe and efficient nanosensitizer for radiotherapy combined with thermal therapy to achieve non-invasive, accurate and efficient treatment of tumors, and promote the application of radiotherapy combined with thermal therapy in clinical treatment of tumors.