硫化钼纳米片的制备、功能化修饰及其时空可控的多效抗肿瘤诊疗研究

The object of this study mainly focus on the demand for effective combating drug-resistant breast cancer based on two-dimensional molybdenum sulfide (MoS2) nanosheets with unique properties including large surface area, effective antitumor drug loading ratio as well as high near infrared (NIR) photothermal conversion efficiency. However, low yield and large size of the as-synthesized MoS2 nanosheets are still serious problems which need to be addressed. Therefore, this study is expected to solve these problems on the basis of a simple synthesis route, surface functionalization modification to construct an intelligent nano-drug delivery system. This multifunctional nanocarrier platform not only has good biocompatibility but also can effectively target breast tumor and reverse the drug resistance. The effects of synthesis conditions on the sizes and photothermal conversion efficiency will be further investigated. Using the combination of targeting and NIR 808 nm photothermal therapy will realize spatio-temporal controllable drug release from the MoS2 nano-vector in the cells. The reversal drug-resistant mechanism of the targeting combined thermotherapy on the breast cancer will be revealed. Meanwhile, based on the advantages of simple and high efficient labeling 64Cu on the surface of MoS2, positron emission tomography (PET) imaging can real-time detect the treatment effect and regularity of the MoS2 nanoplatform on the drug-resistant tumor mice to realize the integration of diagnosis and treatment. The research will provide a new idea to make MoS2 for improving theranostic application of the drug-resistant breast cancer.

本项目拟用层状纳米硫化钼比表面积大利于抗肿瘤药物负载和近红外光热转换效率高的特点，以耐药乳腺肿瘤有效治疗的需求为目标，抑制肿瘤耐药为切入点，针对合成中纳米片产率低、尺寸大的问题，在用简单合成路线高产率制备尺寸可控的硫化钼纳米片的基础上，进行表面功能化修饰并负载抗肿瘤药来构建新型智能纳米硫化钼载药体系，预期得到集‘生物相容性好、可高效靶向乳腺耐药肿瘤、逆转耐药效果好’于一体的多功能纳米载药平台，深入研究制备条件对材料尺寸和热效应的影响规律，利用靶向-近红外808nm光热联合治疗的策略，实现该纳米药物载体在细胞内的定点、定时智能光控释药，揭示靶向联合热疗对耐药乳腺肿瘤的逆转耐药机制和相关规律，同时，结合硫化钼纳米片表面可进行简单高效64Cu标记的优势，用正电子发射断层（PET）成像示踪该纳米复合载体对耐药肿瘤小鼠的治疗效果和规律，实现诊疗一体化，为提高耐药乳腺肿瘤的诊断和治疗效果提供了新思路。

本项目利用层状纳米硫化钼比表面积大利于抗肿瘤药物负载和近红外光热转换效率高的特点，以耐药乳腺肿瘤有效治疗的需求为目标，抑制肿瘤耐药为切入点，针对合成中纳米片产率低、尺寸大的问题，在用简单合成路线高产率制备尺寸可控的硫化钼纳米片的基础上，进行了表面功能化修饰并负载抗肿瘤药来构建新型智能纳米硫化钼载药体系，得到了集生物相容性好、可高效靶向乳腺耐药肿瘤、逆转耐药效果好’于一体的多功能纳米载药平台，深入研究了光热效应规律，利用靶向-近红外808nm光热联合治疗的策略，实现了该纳米药物载体在细胞内的定点、定时智能光控释药，揭示了靶向联合热疗对耐药乳腺肿瘤的逆转耐药机制和相关规律，同时，结合硫化钼纳米片表面可进行简单高效64Cu标记的优势，用正电子发射断层（PET）成像示踪了该纳米复合载体对耐药肿瘤小鼠的治疗效果和规律，实现诊疗一体化，为提高耐药乳腺肿瘤的诊断和治疗效果提供了新思路。本项目顺利完成了任务书中的预期研究目标。在本项目的资助下，共发表SCI论文17篇，其他论文3篇。申请中国发明专利4项，其中授权2项。培养研究生8名。项目负责人参加国内外学术会议10次，其中4次为邀请报告，邀请高能所外专家来所内进行学术交流1次。项目负责人获得2018年纳米药物国际会议（ChinaNanomedicine 2018）的最佳口头报告奖。