高输送量的靶向热化疗给药体系的构建及联合抗肿瘤研究

纳米递药体系的研究中，载体的载药量低、靶向性差是影响药物疗效的关键因素。本项目利用药物与载体整合化思路，以及表面工程化技术，构建具有“肿瘤靶向”、 “高输送量”的热化疗给药体系，用于肿瘤的联合治疗。将合成的聚多巴胺纳米粒充当热疗药物，以及化疗药物阿霉素的载体，并将核酸适配体AS1411修饰于纳米药物表面，同时提高热疗与化疗药物的载药量，以及输送到肿瘤的药量，有望显著提高疗效。 利用 TEM、DLS、共聚焦显微镜、荧光探针等技术表征体系的形貌特点与细胞摄取过程，研究影响载药量和靶向性的理化因素；利用肿瘤小鼠模型，监测各时间段的药物分布与肿瘤生长，揭示靶向性、高输送量与抗肿瘤效果之间的关系。这一体系解决了向肿瘤高输送两种药物的困难，为肿瘤联合治疗提供新的治疗方案。

In nanomaterial research for drug delivery, low drug loading and poor targeting are key factors affecting drug efficacy. In this project, a drug delivery system used in tumor combination treatment characterized by " tumor-targeted" and " high-delivery " will be constucted through medicine-carrier integration strategy and surface engineering technology . Polydopamine nanoparticles will be synthesized as thermotherapy agent as well as chemotherapy drug (doxorubicin) carrier, with aptamer AS1411 modified on the surface of the nanoparticles. It can improve the drug loading of two drugs and their tumor-delivery doses, which is expected to significantly improve the therapeutic effect. The TEM, DLS, confocal microscopy and fluorescence probe techniques are used to characterize the morphology characteristics and cellular uptake process, to study the influence of physicochemical factors on the drug loading and tumor-delivery dose. The relationship between the drug loading, tumor-delivery dose and the anti-tumor effect is revealed by monitoring the drug biodistribution and tumor growth in mice tumor model. This system solves the problem of high delivery of two drugs to tumor, which provides a new approach for tumor combined treatment.