以白蛋白为模板构建肿瘤靶向的近红外光学/磁共振成像和基因治疗一体化探针

Theranostic nanoparticles integrated molecular imaging and therapy, capable of diagnosis, therapy of malignant diseases (such as cancer) and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicines, so it is highly desired to develop theranostic probes with excellent biocompatibility to improve its clinical application. BSA is an excellent template with the merits of versatile functional groups, good water solubility and excellent biocompatibility, which has been used extensively to fabricate low toxic molecular imaging probes and gene delivery carriers. However, no work on fabrication of theranostic probes using BSA as template has been reported so far. Here, we aim to develop folic acid and polyethyleneimine modified BSA-Au nanoclusters (or Gd2O3/Gd(OH)3 nanoparticles) for tumor-targeted near-infrared fluorescent (or magnetic resonance) imaging and gene delivery in vivo, in which low molecular weight PEI with low toxicity was conjugated to BSA molecular to improve gene transfection efficiency. A “see and treat” approach could be used in vivo by utilizing the proposed theranostic probe with excellent biocompatibility as a single agent for both imaging and therapy. The project will promote the further development of low-toxic theranostic probes for diagnosis, treatment and evaluation of therapy of cancer.

诊疗一体化纳米探针可以对重大疾病（如肿瘤）实现同步成像和治疗，通过成像来监测治疗效果以便适时调整治疗方案。因此，开发具有良好生物相容性的诊疗一体化探针具有重要意义。BSA作为一种官能团丰富、水溶性好、生物相容性好的优良模板，在低毒分子成像探针和基因转染载体的构建方面应用广泛，但是以其为模板构建诊疗一体化分子探针还未见报道。本项目拟以BSA为模板，引入成像（荧光金纳米簇或Gd2O3/Gd(OH)3纳米粒子）和基因转染单元（低分子量PEI），在保持低分子量PEI生物毒性低的优势的同时，通过提高探针表面正电荷密度提高转染效率。通过靶向识别分子-叶酸的修饰构建低毒的靶向近红外荧光（磁共振）成像和基因治疗一体化分子探针。本项目对于进一步发展低毒诊疗一体化探针用于研究癌症的发展历程、诊断、治疗和疗效评价等具有重要的意义。

诊疗一体化纳米探针可以对重大疾病（如肿瘤）实现同步成像和治疗，通过成像来监测治疗效果以便适时调整治疗方案。因此，开发具有良好生物相容性的诊疗一体化探针具有重要意义。仿生技术为人类科学技术的发展起到了极大的推动作用，但在生命科学领域的应用亟需深度拓展。本项目主要研究以蛋白为模板的仿生学方法在构建纳米成像和治疗探针中的应用。通过模拟生物矿化和血清蛋白运输功能，引入新兴的治疗和免疫治疗方法，在温和条件下以蛋白为模板高效制备了若干生物相容性良好的生物成像和治疗探针。提出了模仿药物-底物相互作用的新型仿生策略用于构建高效的肿瘤诊疗一体化纳米平台。本项目为简易制备性能优良和生物安全性良好的生物成像和治疗探针提供了新方法，对于发展具有临床应用潜能的诊疗探针起到一定的推动作用。