诊疗一体化多功能纳米探针的研制及其在多模态影像引导下卵巢癌精准治疗研究

As a new technology, cancer theranostics, which combines the modalities of therapy and diagnostic imaging, can conquer the technique limit of single modality, and achieve the diagnostic and therapeutic purpose simultaneously. The design and synthesis of theranostics molecular probes is the core technology for the cancer theranostics. We design a multifunctional copper sulfide nanoparticle platform for cancer theranostics, which combined 4 imaging modalities (including positron emission tomography, magnetic resonance imaging, photoacoustic imaging, and Cherenkov imaging) and 2 therapeutic effects (including photothermal therapy and radionuclide therapy), simultaneously. First, the integration of 64Cu to the copper sulfide nanoparticles homologously make the nanoparticles suitable for PET imaging, Cherenkov imaging, and radionuclide therapy. Then, the MRI function can be achieved by doping of manganese to the result nanoparticles. The prepared nanoparticles also can be used for photothermal therapy of cancer due to their strong absorption in near-infrared region. The conjugation of folic acid on the nanoparticle surface can significant improve the tumor uptake. Four imaging modalities can overcome the limit of one single modality, and provide accurate image information with high-sensitive and high-resolution, and also monitor the changes and therapeutic effects during the treatment. One the other hand, under the multimodal imaging guidance, the combination therapy can accurate targeted destroy the ovarian cancer cells owing to the synergistic effect of photothermal therapy and radionuclide therapy. This project develop a new strategy and new method for cancer diagnostic and therapy, and has great opportunity to improve the therapeutic effect of cancer treatment.

癌症的诊断和治疗一直是科学界的一个难题，诊疗一体化是把诊断和治疗两者有机同步地结合起来，以实现在诊断的同时达到治疗的目的。其中诊疗一体化分子探针的研发被视为实现癌症诊疗一体化的核心技术与科学前沿。我们通过同源性导入核素Cu-64到硫化铜纳米材料中，并在合成过程中高效掺杂锰，同时利用叶酸对其进行表面修饰，构建一种可同时用于PET、核磁共振、光声、切伦科夫发光等四种模态成像，并可用于肿瘤光热及核素放射联合治疗的靶向多功能诊疗一体化硫化铜纳米探针。其中四模态成像既可解决各自单一成像的不足，提供高灵敏度、高空间分辨率的精准成像信息，亦可对治疗效果进行有效的监测。该纳米探针又可以同时实现肿瘤光热与核素放射两种治疗方式，通过相互协同作用，在多模态影像引导下对卵巢癌细胞实施精准地“双重打击与围剿”，实现高效地肿瘤靶向治疗。本项目为癌症的诊断与治疗开拓了新思路、发展了新方法，有望显著提升癌症的治愈效果。

卵巢癌是女性常见的恶性肿瘤之一，其死亡率占各类妇科肿瘤的首位，对妇女生命健康造成严重威胁。由于卵巢的胚胎发育、组织解剖及内分泌功能较复杂，早期症状不典型，术前鉴别卵巢肿瘤的组织类型及良恶性相当困难。所以在早期诊断及有效治疗上是当前一大科学难题。多模态、多功能诊疗一体化纳米探针在肿瘤诊疗一体化及精准治疗方面具有突出优势，主要表现为：（1）可通过多种医学影像方式对药物进行实时监测，有效控制药物的治疗效果；（2）可同时具有肿瘤治疗效果，集诊断与治疗于一体；（3）可进行化学修饰，提高靶向性。因此，新型诊疗一体化分子探针在卵巢癌肿瘤具有较好的应用前景，有望实现肿瘤的早期发现、精确诊断、靶向治疗，为肿瘤临床诊断及治疗带来新的突破。本研究中旨在研发新型诊疗一体化纳米探针，实现多模态成像，并在多模态影像引导下实现肿瘤高效治疗。.本研究结果发现如下：..1..制备多种多模态分子影像探针，实现PET、核磁共振、光声等多模态成像，并可用于肿瘤光热及核素放射联合治疗。.2..其中多模态成像既可解决各自单一成像的不足，提供高灵敏度、高空间分辨率的精准成像信息，亦可对治疗效果进行有效的监测。.3..该纳米探针又可以同时实现肿瘤光热与核素放射两种治疗方式，通过相互协同作用，在多模态影像引导下对卵巢癌细胞实施精准地“双重打击与围剿”，实现高效地肿瘤靶向治疗。.4..本项目通过多模态纳米探针的研发，并结合新型治疗技术，为卵巢癌肿瘤的诊断与治疗开拓了新思路、发展了新方法，有望提升癌症的治愈效果。