多功能纳米探针的构建及其用于多模态分子成像引导下的肿瘤光热治疗的研究

In recent years, nano-materials make a breakthrough in the field of biomedical, especially nano-materials as imaging contrast agents and drug carriers were approved for clinical application and bring new hope to tumor treatment. The fascinating physical and chemical properties of nanomaterials can integrate a variety of imaging contrast agents and pharmaceutical preparations, and then we can achieve the integration of cancer diagnosis and treatment and open a new page for the targeted molecular imaging and treatment. The study of multimodal molecular imaging is still in its infancy at home and abroad,and it is rarely reported that the nanoprobes of multimodal molecular imaging guided photothermal therapy(PTT) have good clinical prospect. We therefore strategically select and use biocompatible materials of gold nanorods (GNRs) and melanin nanoparticles (MNPs), proposed to design and synthesize a new core-shell structure of GNRs@MNPs. By grafting RGD peptide and chelating Gd3+ and radionuclide 64Cu, we integrated multi-functional of MNPs and GNRs cleverly, not only enhances the signals of photoacoustic and the specificity of targeted tumor, but also could achieve three-mode molecular imaging(MRI/PET/PAI) guided tumor-targeted photothermal therapy, respectively. The new multifunctional nanoprobe can achieve tumor multimodal molecular imaging and early accurate diagnosis of the tumor. Meanwhile it could achieve image-guided treatment and efficacy monitoring. Finally，we will accomplish the integration of tumor diagnosis, treatment and efficacy monitoring, which will provide a new way to explore new methods of cancer diagnosis and treatment.

纳米材料在生物医学领域不断突破，特别是纳米材料作为成像造影剂和药物载体被批准应用于临床，为癌症诊疗注入了新的希望。纳米材料独特的理化性质可将多种造影剂和药物制剂整合于一体，实现癌症的诊疗一体化。国内外对多模态成像和诊疗一体化的纳米探针研究尚处于起步阶段，对于有良好转化前景的多模态分子成像引导光热治疗的纳米探针更是鲜有报道。本项目选用生物相容性好的金纳米棒(GNRs)和黑色素纳米颗粒(MNPs)，构建新型结构的GNRs@MNPs，并通过嫁接RGD肽和螯合Gd3+和核素64Cu，巧妙整合了MNPs和GNRs的功能，增强了光声信号和肿瘤靶向性，实现了三模态分子成像(MRI/PET/PAI)引导下的肿瘤光热治疗。这种新型的多功能纳米探针既可以实现肿瘤的多模态分子成像，对肿瘤进行早期、精准诊断；又能图像引导下治疗和疗效监测，实现肿瘤的诊断、治疗、疗效监测一体化，为探索癌症诊疗的新方法提供了新的思路。

喉癌具有高度的侵袭性，且对传统的靶向治疗不敏感，这往往导致其治疗效果欠佳。影像引导下精准治疗是一种具有前景意义的肿瘤治疗策略。与传统疗法相比，它具有更高的安全性和有效性。在这里，我们提出了一种基于黑色素涂层金纳米棒（GNR）的诊疗一体化纳米探针，该探针具有良好的多模态成像能力和光热效应，可适用于多模态光声（PA）/正电子发射断层扫描（PET）/磁共振（MR）成像引导下的喉癌光热治疗。由于其自身具有良好的生物相容性和对金属离子的强亲和力，黑素纳米颗粒显著抑制了模板十六烷基三甲基溴化铵双层的细胞毒性，并使GNR具有优异的PET/MR成像性能。此外，GNR的引入极大地提高了黑色素纳米颗粒的近红外吸光度和被动靶向能力，使其具备了出色的PA成像和肿瘤光热消融能力。该纳米探针在生理条件下具有高稳定性和分散性。经静脉注射后，纳米探针可在体内对肿瘤进行精确示踪，使喉癌的定位和成像成为可能。同时，联合光热疗法可有效地切除肿瘤且副作用很小。因此，这项工作提供了一种具有良好生物相容性的多模态成像下高抗肿瘤光热治疗的纳米探针，在喉癌治疗中具有极小的副作用，这对于推动纳米材料在癌症诊疗的临床转化具有重要意义。