基于超声响应型纳米诊疗剂的脑胶质瘤声化疗协同治疗研究

This project aims at the brain glioma diagnosis and treatment system facing the glioma high infiltration, the boundary is unclear, poor drug targeting, poor penetration of the blood-brain barrier and other major issues, we design a collection of tumor-targeting, blood-brain barrier penetrating, ultrasound response and activatable functions as nano diagnostic and therapeutic agents with both diagnosis and treatment..Based on previous experiments of ultrasound combined with microbubbles in the diagnosis and treatment of glioma, the project group is going to build a multi-modal molecular probe that combines fluorescence, photoacoustic and magnetic resonance imaging: using nano-liposomes as the matrix, the doxorubicin hydrochloride (Dox) load in the shell, connecting sonosensitizer two chlorin E6 (Ce6), in addition, the surface of the nanoparticles was conjugated with the tLyp-1 targeting peptide, to achieve the targeted ultrasound-guided glioma treatment of glioma synergistic and ultrasound-activated anti-cancer drug-specific controlled release in order to verify the nano-particles and acoustic dynamic collaborative diagnosis and treatment of glioma efficiency and prospects for conversion. Based on the new viewpoint of nano-biotechnology to enhance the dynamic therapy of acousto-acoustic therapy, this study applied nano-sensitizer combined with acousto-dynamic in brain glioma model to realize multimodality molecular imaging and therapy of glioma in vivo, providing a new idea and new means for accurate imaging and targeted therapy.

针对脑胶质瘤诊疗中面临的肿瘤高浸润性、边界不清、药物靶向性差、血脑屏障穿透性差等关键科学问题，设计一种集肿瘤靶向性、血脑屏障穿透性、超声响应和可激活功能兼具诊断和治疗为一体的纳米诊疗剂。本项目组在前期超声联合微泡诊疗脑胶质瘤体内外实验的基础上，拟构建一种集荧光、光声和磁共振成像的多模态分子探针：以纳米脂质体为基体，利用其两亲性，内负载盐酸阿霉素（Dox），壳层连接声敏剂二氢卟吩e6（Ce6），并在表面修饰靶向胶质瘤细胞的多肽tLyp-1，实现靶向超声导航的胶质瘤声动力学治疗增效和超声激发抗癌药物特异性的可控释放，以期验证该纳米颗粒与声动力协同诊疗脑胶质瘤的有效性与转化前景。本研究立足纳米生物技术增强声动力疗法的新视点，将纳米声敏剂与声动力联合应用于脑胶质瘤模型，实现对脑胶质瘤在体多模态分子显像与治疗，为肿瘤精准成像和靶向治疗提供一种新思路与新手段。

为了克服脑胶质瘤诊疗中面临的肿瘤高浸润性、边界不清、药物靶向性差、血脑屏障穿透性差等关键科学问题，本项目团队通过基于湿化学合成方法的机制设计二维硅烯纳米片（silicene）。该纳米材料具有较强的光稳定性和优异的产氧能力，与c(RGDyC)结合后(标记为SRGD)具备良好的生物相容性和特异靶向性，成为一种集肿瘤靶向性、血脑屏障穿透性、光响应性兼具诊断和治疗为一体的纳米诊疗剂。在激光的照射下，产生具有线粒体损伤的活性氧(ROS)，能够有效杀伤肿瘤细胞。在光声成像的监测/引导下，实现了有效的体内光动力治疗抗肿瘤效果，此外，c(RGDyC)产生的特异性癌细胞靶向特性，以αvβ3整合素的过表达为特征，对特异性肿瘤微环境具有优异的光动力治疗选择性，进一步促进了该纳米剂抑制肿瘤生长的效率，与对照组比较，SRGD+激光组对肿瘤的抑制率达到88.7%。综上所述，本研究为肿瘤精准成像和靶向治疗提供一种新思路与新手段。.