目前研究认为血脑屏障的存在及不能有效阻断肿瘤血供是导致胶质瘤化疗疗效不佳的重要因素，因此，研发可携带化疗药物和抗血管生成药物跨越血脑屏障的新型载药系统可能是提高胶质瘤化疗疗效的有效途径。我们前期研究中报道了肝素纳米载药系统在血液模拟环境中发生重新自组装导致粒径变小，从而有利于其跨血脑屏障的特性。本研究拟应用可重新自组装的肝素纳米载药系统，负载具有双重阻断血供作用的cRGD导向肽，并针对胶质瘤微环境呈弱酸性和还原性的特点，设计PH敏感的腙键和还原敏感的二硫键，将阿霉素偶联到肝素上，制备能跨血脑屏障在胶质瘤组织中精确快速释放药物的纳米药物复合体，体外检测该复合体的生物活性，并在原位胶质瘤和原位胶质瘤手术切除后动物模型上评估其在体疗效，同时探讨该复合体在血液环境中重新自组装及杀伤肿瘤的作用机制。本研究有望提高胶质瘤化疗疗效、丰富胶质瘤治疗药品种类，该研究方法可能为靶向胶质瘤的药物研发提供新思路。

The presence of the blood-brain barrier (BBB) and incapable of efficiently blocking the blood flow in glioma are considered as leading causes of poor glioma chemotherapy effects by current studies. Therefore, the development of novel drug delivery systems carrying chemotherapeutic and anti-angiogenesis drugs across the BBB for glioma treatment might be a promising way to enhance the efficiency of glioma chemotherapy. In previous work, we reported heparin-based nanoparticle delivery system could re-self-assemble in blood-mimic condition, leading to a smaller size helps to cross the BBB. In this study, we aim to apply the re-self-assembly heparin-based nanoparticles to load cRGD targeting peptides with dual blocking blood supply, and then fabricate nanoparticle drug complex can across the BBB and accurately rapid release drugs in glioma, through conjugate doxorubicin to heparin with PH-sensitive hydrazine bond and reduction-sensitive disulfide bond for targeting to the reducing acidic microenvironment of glioma. Afterwards, detect the biological activity of the nanoparticle complex in vitro, and investigate the in vivo efficacy of the complex in intracranial xenograft glioma and glioma surgical resection animal models. Finally, further study the mechanism of re-self-assembly in blood condition and anti-glioma effect of the complex. This study is hopeful for improving glioma chemotherapy efficacy and enlarging kinds of glioma drugs, the research method might provide new ideas for the development of drugs target to glioma.