用于肿瘤多靶点药物协同治疗的多功能聚合物载体材料研究

项目名称： 用于肿瘤多靶点药物协同治疗的多功能聚合物载体材料研究

项目编号： No.U1401242

项目类型： 联合基金项目

立项/批准年度： 2015

项目学科： 管理科学

项目作者： 帅心涛

作者单位： 中山大学

项目金额： 241万元

中文摘要： 针对癌组织的多细胞组成、多网络调控因子、复杂微环境（低氧、低pH和高间质压等）进行多药联合治疗是改善治疗效果的重要手段，关键在于发展满足特殊药物输送性能要求的多功能载体材料，克服常规多剂型药物联合治疗方法的给药操作复杂、药物的剂量和作用时间难以调控等缺陷。拟制备具有肿瘤多靶点智能输药功能的纳米载体材料，采用物理包载、共价偶联以及主客体识别等手段，将分别作用于肿瘤细胞和肿瘤基质的多种药物共负载到同一个纳米载体上，通过对肿瘤基质和肿瘤细胞内多重微环境刺激敏感的载体理化结构来控制药物释放，使所负载的不同药物按照所设定的释放时间次序被分别释放到所对应的肿瘤基质和肿瘤细胞，实现多靶点药物协同作用，改善肿瘤药物治疗的效果。此外，将通过载体粒径控制、癌组织渗透肽iRGD修饰等措施，赋予载体长循环以及高效癌组织穿透性能，提高癌组织内药物的浓度和分布范围，进一步改善肿瘤治疗效果。

中文关键词： 肿瘤治疗；多治疗靶点；纳米药物；聚合物载体材料；控制释放

英文摘要： Combined multi-drug treatment acting on different cell types, multiple networking regulation factors and complex microenvironment (hypoxia, low pH and high interstitial pressure etc.) is an important approach to improve the therapeutic effect. The key is to develop multifunctional carrier materials that meet the special property requirements for drug delivery to overcome the drawbacks of conventional combinatory therapy adopting multiple drug formulations, e.g. complicated drug administration, difficulty in regulating drug dose and action time. Nanocarrier materials which can intelligently deliver drugs to tumor multi-therapeutic targets will be prepared. Multiple drugs separately acting on tumor cells and tumor extracellular matrix will be co-loaded into one nanocarrier using methods such as physical entrapment, covalent conjugation and host-guest recognition etc. Drug release will be controlled by carrier physicochemical structure which is sensitive to multiple stimuli of tumor matrix and intracellular microenvironments. Consequently, different drugs loaded into the nanocarrier will be separately released into their aimed tumor matrix and tumor cells following a programmed time-sequential release pattern, resulting in multi-drug synergistic action on multi-therapeutic targets which is expected to improve the outcome of tumor drug therapy. In addition, carrier will be endowed with properties of long circulation and effective tumor tissue penetration via carrier size control and modification with tumor-penetration peptide iRGD to increase intratumoral drug concentration and distribution area for further improved therapeutic effect.

英文关键词： NULL