双重靶向诊疗剂用于FL/MR/PA三模态成像指导的协同治疗研究

Cancer theranostic is a research hotspot and challenge. In this project, we will design and prepare a RGD peptide conjugated magnetic melanin nanoparticles (RGD-MMNs) that can co-load chemotherapeutic drug doxorubicin (DOX) and indocyanine green (ICG) for fluorescence (FL), magnetic resonance (MR), and photoacoustic (PA) tri-modal imaging guided dual-targeting chemo-photothermal synergistic therapy of U87MG glioblastoma cancer. The bioploymer melanin is used as the biotemplate to direct the synthesis of magnetic nanoparticles by biomimetic synthesis method. RGD is then conjugated with MMNs. The cross-link indole rings of melanin promise the co-loading of DOX and ICG via π–π stacking. Based on the dual-targeting effect of RGD-involved active targeting and magnet field-induced physics targeting, the tumor accumulation rate of RGD-MMNs-DOX-ICG could be efficiently improved. Upon dual stimuli of tumor acid microenvironment and laser irradiation, the control release of DOX and ICG could be achieved with "off-on" fluorescence recovery for tri-modal imaging guided chemo-photothermal synergistic therapy. In this study, one nanoplatform allows to combine RGD active targeting with magnetic targeting, and integrate chemotherapy and photothermal therapy together, which enables early diagnosis, accurate positioning, efficient therapy, real-time monitoring treatment response of U87MG glioblastoma cancer.

癌症诊疗一体化是研究热点和难点。本项目拟设计和制备RGD多肽共轭的磁性黑色素纳米颗粒（RGD-MMNs），然后共装载化疗药物阿霉素（DOX）和吲哚菁绿（ICG），用于神经胶质瘤（U87MG）的FL/MR/PA三模态成像介导的双重靶向化疗和光热协同治疗。利用黑色素作为模板仿生法合成MMNs，然后共价偶联RGD。利用黑色素的吲哚环结构，π-π堆积装载DOX/ICG。通过RGD介导的主动靶向和磁场引导的物理靶向相结合的双重靶向作用，提高纳米药物在肿瘤部位的蓄积效率。在肿瘤酸性微环境和光照双重刺激作用下，实现DOX/ICG的可控释放，ICG荧光“淬灭-恢复”实现“off-on”荧光成像, 最终实现三模态成像监控的化疗和光热协同治疗。本研究利用纳米技术平台创新性地融合双重靶向实现肿瘤的协同治疗，有望为解决U87MG的早期诊断、精确定位、高效治疗、疗效实时监测等关键科学问题提供理论和技术基础。

癌症诊疗一体化是研究热点和难点。本项目设计和制备RGD多肽共轭的磁性黑色素纳米颗粒（RGD-MMNs），然后共装载化疗药物阿霉素（DOX）和吲哚菁绿（ICG），用于神经胶质瘤（U87MG）的FL/MR/PA三模态成像介导的双重靶向化疗和光热协同治疗。利用黑色素作为模板仿生法合成MMNs，然后共价偶联RGD。利用黑色素的吲哚环结构，π-π堆积装载DOX/ICG。通过RGD介导的主动靶向和磁场引导的物理靶向相结合的双重靶向作用，提高纳米药物在肿瘤部位的蓄积效率。在肿瘤酸性微环境和光照双重刺激作用下，实现DOX/ICG的可控释放，ICG荧光“淬灭-恢复”实现“off-on”荧光成像, 最终实现了三模态成像监控的化疗和光热协同治疗。本研究利用纳米技术平台创新性地融合双重靶向实现肿瘤的协同治疗，有望为解决U87MG的早期诊断、精确定位、高效治疗、疗效实时监测等关键科学问题提供理论和技术基础。