抗体修饰的GQA纳米载体搭载Fe3O4和阿霉素穿血脑屏障指导高级别胶质瘤的手术切除范围及术后化疗的实验研究

How to improve the efficacy of clinical treatment for high grade gliomas is currently the direction in which many neuro-oncologists make arduous efforts constantly. Surgical resection is still the most critical first step of all kinds of combined treatment strategies. However, since it is difficult to judge the histopathologic boundary of high grade gliomas, which should be attributed to diffuse infiltrative characteristics, neurosurgeons often worry about making operation plan. In addition, most of the drugs cannot reach the target by penetrating through the blood brain barrier to treat the diseases in the central nervous system. Therefore, the current situation of the efficacy of clinical treatment for high grade gliomas is not satisfactory. This study will prepare a nano-carrier that can integrate the efficacy of diagnosis and treatment, by which a GQA-polyurethane nanocarriers synthesized previously take up Fe3O4 and doxorubicine, and coupling a GPNMB-antibody which have high expression level in high grade gliomas. We expect the nano-carrier is able to outline the histopatho- logic boundary of high grade gliomas more accurately, by penetrating through the blood brain barrier. As a result, it may guide the scope of surgical removal and continue the postoperative chemotherapy. This study will provide new ideas and choices for the treatment of high grade gliomas, and lay the theoretical foundation for future clinical application.

如何提高高级别胶质瘤的临床治疗效果是目前神经肿瘤学领域不断努力奋斗的方向。外科手术切除依然是脑胶质瘤综合治疗策略中最为关键的第一步,但由于其弥漫浸润性生长的特性，对肿瘤组织病理学边界判断的模棱两可，依然是限制外科医生手术计划制定的瓶颈。并且,大多数治疗中枢神经系统疾病的药物因受限于血脑屏障，因此高级别胶质瘤临床治疗效果的现状不尽人意。本研究拟采用既往合成的一种GQA纳米载体搭载Fe3O4和阿霉素,并且偶联一个在胶质瘤上高表达的分子靶标GPNMB的抗体，制备成一种集诊断治疗一体化的纳米载体。期望该载药系统能够穿透血脑屏障，勾勒出相对准确的肿瘤组织病理学边界，从而指导高级别胶质瘤的手术切除范围，且利用残余阿霉素继续术后化疗。本研究有望为高级别胶质瘤的治疗提供新的思路和选择，为将来纳米载体应用于临床治疗奠定了理论基础。

争取最大范围的安全切除肿瘤仍是延长患者生存期的最重要手段。高级别胶质瘤呈弥漫浸润性生长，缺乏肉眼可分辨的组织学边界，在手术过程中对于脑胶质瘤切除程度的判断仅依靠外科医生经验和视觉观察往往是不准确的，目前手术切除范围也仅限于肿瘤的影像学边界。本研究采用既往合成的一种GQA纳米载体搭载Fe3O4和阿霉素,并且偶联一个在胶质瘤上高表达的分子靶标GPNMB的抗体，制备成一种集诊断治疗一体化的纳米载体。该载药系统能够穿透血脑屏障，勾勒出相对准确的肿瘤组织病理学边界，从而指导高级别胶质瘤的手术切除范围，且利用残余阿霉素继续术后化疗。本研究有望为高级别胶质瘤的治疗提供新的思路和选择，为将来纳米载体应用于临床治疗奠定了理论基础。