光电磁响应铁电/铁磁二硫化铼纳米体系的构建及其在肿瘤诊疗中的应用

Multimodal cancer theranostics are able to complement limitations of individual theranostics to achieve a better efficacy. Owing to ulrahigh specific surface area and low in vivo toxicity in human, ReS2 possesses high potential for clinical application. ReS2 generates heat from light irradiation, leading to photoacoustic imaging-guided photothermal therapy. Compared to light irradiation, magnetic field and electric field permit no depth-penetration limit in the human body and precise control over the magnitude, duration, and intervals of pulses. Under magnetic and electric stimulus, magnetic and ferroelectric nanosystem can be used for magnetic targeting for drug delivery, magnetic resonance imaging, hyperthermia, and controlled release of drug molecules, thereby improving theranostic accuracy and efficacy. Recently, we have acquired phase-engineering ferroelectric and ferromagnetic ReS2 microsheets in a simple way. On this basis, it is necessary to further reduce size and modify suface with PEG to improve the biocompatibility of ReS2, which will have an effect on microstructure and performance. In this project, differently sized multiferroic ReS2 nanosystems capped by polyethylene glycol (PEG) ligands through different anchoring groups will be prepared. Combining experiments with theoretical simulation, the influence of the microstructure on magnetism and ferroelectricity as well as the regulation effect of magnetoelectric performance on theranostic efficiency will be explored, in order to unveil the relationship among the microstructure, magnetoelectric performance and theranostic efficiency. Thus, the study will provide the basis for the design of the microstructure to improve theranostic efficacy. In the current project, a simple method is used to prepare multiferroic rhenium disulfide nanosystem for multimodal cancer theranostics, which provides a novel strategy to fabricate multimodal cancer theranostic nanosystems and deepens knowledge of two-dimensional materials. Thus, this project has considerable value on promoting the development of multimodal cancer theranostics.

单一诊疗模式在肿瘤诊疗中存在效率低的问题，多模态诊疗是研究的趋势。ReS2比表面积大、体内毒性低，光照下，可用于光声成像和光热治疗。较之于光，磁场和电场没有穿透深度的限制且易于操控，在二者作用下，具有磁性和铁电性的纳米体系可以实现靶向递药、磁共振成像、磁热、电热和可控释药等，从而提高诊疗效率。该项目在本课题组最近已获得具有铁磁和铁电ReS2微米层的基础上，为了实现多模态诊疗，进一步构筑PEG修饰的ReS2纳米体系，研究尺寸、PEG末端官能团类型对其微结构和电子、自旋结构的影响，结合实验和理论，揭示微结构影响磁电性能的本质以及磁电性能与诊疗效果的关系，以磁电性能为桥梁，建立微结构和诊疗效果的联系，从而通过材料优化来实现诊疗效率的提高。该纳米体系制备简单，融入新的物理效应，提出了一种实现多模态诊疗的新途径，对肿瘤多模态诊疗的发展具有一定的推动作用。

目前癌症的生存率较低，这主要由诊断时间晚、治疗效果不理想所致。为此，诊疗一体化的概念引起了广泛关注。纳米材料具有光、电、磁、热等特性，在实现诊疗一体化方面优势显著。本项目深入研究了二维材料的电子和自旋结构，利用轨道杂化、缺陷工程、阴阳离子交换、热电子注入、表面工程等方法对体系的电子和自旋结构进行了精妙调控，建立了微结构与荧光、磁性性能的关系，系统阐释了荧光和磁性调控的机理，实现了二维材料可调谐的荧光、磁性、拉曼增强等性能，从而进一步赋予了它们荧光成像、磁共振成像、拉曼成像、磁靶向、磁热治疗等功能，有效拓展了它们的诊疗模式。在此基础上，也对它们的诊疗性能进行了进一步研究。主要包含以下几个方面的成果：.（1）基于轨道杂化的原理，P=O键通过可控的氧化过程被引入到黑磷纳米片中，实现了荧光和室温铁磁性的共存。具有良好的生物相容性的黑磷体系可以实现磁共振、光声、荧光三模成像指导的光热、磁热治疗。.（2）利用阴阳离子交换的新策略，增强了ReS2的室温铁磁性。该策略为进一步提升ReS2的磁共振成像、磁热治疗、磁靶向等诊疗性能提供了有益指导。.（3）我们通过缺陷工程的方法，增强了电场对ReS2各向异性激子的调制。该方法为进一步提升其诊疗性能创造了条件。.（4）我们利用合适的溶剂进行探针超声得到尺寸分布均匀ReS2纳米层，进一步采用mPEG-NH2修饰，得到具有1.2 emu/g饱和磁化强度的诊疗剂。该诊疗剂在光声、CT成像和光热治疗的基础上，进一步拥有靶向递药、磁热以及磁共振成像指导的治疗等性能。.（5）利用激发态效应，实现了T@Td-ReS2薄膜的激子共振。RhB作为探测分子，增强因子高达108，检测限低至10-9 M。此外，T@Td-ReS2基底均匀，在空气中稳定，具有独特的各向异性拉曼增强效应。该结果表明T@Td-ReS2基底可以实现SERS在医学检测中的实际应用。.我们相信上述研究成果对建立微结构与磁电性能的关系，理解磁电调控的机理，开发高效的多模态纳米诊疗剂具有重要的参考价值。