"磁性鸡尾酒"功能型水凝胶用于三阴乳腺癌综合治疗的研究

Triple negative breast cancer (TNBC), a special breast cancer with clinical features of strong invasiveness and poor prognosis, mainly occurs to young women before menopause. It seriously threats to women's health and hence, the development of novel and effective therapeutic approaches to improve both the treatment efficiency and prognosis is highly desired. In this project, a novel ‘magnetic cocktail’ functional hydrogel is proposed as an implantable local treatment device. Vortex magnetic nanodeivce which possessing excellent magnetic/heat transferring efficiency will be adopted as the high-performance mediator for magnetic hyperthermia. The grafting strategy will be employed in the fabrication of the magnetic drug-loaded hydrogel. The hydrogel can be easily injected onto the residual tumor bed after surgical removal of the bulky tumor. Possessing the unique features of self-healing and self-adaptiveness, the hydrogel can fit perfectly with the irregular wound surface to prompt the effect of the contained treatment moieties. The magnetic nanoparticles can act as the thermal mediators for local and accurate hyperthermia treatment upon exposure under the alternative magnetic field. Co-delivery of docetaxel and epirubicin can also be achieved by the hydrogel so as to main a rather high concentration of the combined chemotherapeutic drugs within the tumor site. Moreover, the possible synergistic effect between the magnetic hyperthermia and the combined chemotherapy can be achieved by the functional hydrogel. Aiming to this, the fabrication protocol for the drug loaded ‘magnetic cocktail’ hydrogel will be optimized and its biocompatibility as medical device will be systematically evaluated. Further on, the in-depth investigation of the feasibility of the above-mentioned functional hydrogel as mediator for TNBC thermochemotherapy will be carried out. While the synergistic effect between magnetic hyperthermia and combined-chemotherapy of docetaxel and eprubicin will be elucidated, the relationship between the treatment dosage and the anti-cancer effect will be carefully studied. Briefly, our study will provide useful information for a novel, safe and effective protocol of implantable device for cancer multimodality treatment.

作为一种特殊的乳腺癌，三阴乳腺癌(TNBC)多发生于绝经前的年轻女性，具有侵袭性强、预后差等临床特点。因此，迫切需要研究针对TNBC有效的治疗方法以提高其疗效并改善预后。本课题提出“磁性鸡尾酒”功能型水凝胶的创新植入治疗体系，以网络内部接枝的方法，构建以具有高磁热转化效率的涡旋磁纳米颗粒为热疗介质的、兼具自愈性和自适形性的可注射型磁性载药水凝胶。TNBC肿瘤术后，将此功能型水凝胶均匀注射于瘤床组织，水凝胶的自愈性和自适形性可使介质紧密帖敷瘤床的组织缝隙而不留死角；涡旋磁纳米颗粒可作为肿瘤磁感应热疗的高效介质，对TNBC的术后瘤床实施精确定位的热疗；水凝胶的药物共递送功能可使化疗药物（多烯紫杉醇联合表柔比星）在肿瘤局部维持高浓度；同时，升温可控制并促进化疗药物的共同释放并实现热化疗的协同增敏效应。本研究可为TNBC新型治疗方法提供借鉴和参考，为功能型水凝胶治疗介质的生物医学应用提供新的选择。

乳腺癌是全球女性最常见的恶性肿瘤之一，也是导致女性死亡的重要病因。三阴乳腺癌 (Triple Negative Breast Cancer, TNBC) 对临床常规治疗的敏感性较低，对内分泌治疗以及以曲妥珠单抗为代表的靶向治疗疗效较差，因此临床上一般以化疗为主要治疗手段。目前针对TNBC的临床治疗并无统一标准指导，其治疗一般选择术后辅以放化疗或术前行新辅助化疗。因此，迫切需要研究针对TNBC有效的治疗方法以提高其疗效并改善预后。本课题提出“磁性鸡尾酒”功能型水凝胶的创新植入治疗体系，以网络内部接枝的方法，构建兼具自愈性和自适形性的可注射型磁性载药水凝胶。TNBC肿瘤术后，将此功能型水凝胶均匀注射于瘤床组织，水凝胶的自愈性和自适形性可使介质紧密帖敷瘤床的组织缝隙而不留死角；磁性氧化铁纳米颗粒可作为肿瘤磁感应热疗的高效介质，对TNBC的术后瘤床实施精确定位的热疗；水凝胶的药物共递送功能可使化疗药物（多烯紫杉醇联合表柔比星）在肿瘤局部维持高浓度；同时，升温可控制并促进化疗药物的共同释放并实现热化疗的协同增敏效应，从而实现“一种介质、两种功能、控制释放、协同增敏”的效能。本研究为TNBC术后局部综合治疗功能型高分子基水凝胶载药体系的研究提供新思路。