多功能化药物和siRNA共载体系的制备及抗肿瘤研究

Combining with chemotherapy and gene therapy is an effective treatment of tumors, which has attracted much attention in the field of cancer treatment. However, the traditional drug carriers can't overcome the multistage biological obstacles in the transmission process in vivo, and deliver both drugs and genes to tumor cells at the same time. The project designed a multifunctional drug and gene delivery system for the combined anti-tumor therapy. The co-delivery system has the following characteristics: (1) The complex formed with biodegradable multi-armed grafting cationic copolymers MP-g-OEI and siRNA as the inner core; (2) Synthesis of prodrug Pt(IV) with multiple functions of the charge flipping polymers as the shielding systems. Each component of the shielding systems will be freely adjusted, for realizing the function that the shielding systems possess negative charge in the transfer process in vivo, while positive charge in tumor tissue. Afterwards, the synergistic antitumor effect of chemotherapy drug and gene can be achieved; (3) When the low toxic prodrug Pt(IV) are transferred into tumor cells, Pt(IV) will be reduced into the high antitumor activity of Pt(II) and kill the tumor cells. The project will verify the action of each functional component in co-delivery systems in the transmission process, and comprehend the mechanism of synergistic effect of chemotherapeutic drugs and siRNA. To improve the effect of tumor treatment, the diverse ratios of each functional component and assembly method will be carried out in the project.

化疗药物和基因药物相结合是治疗肿瘤的有效方式，在癌症治疗领域获得了高度重视。传统的药物载体由于无法有效克服体内传输过程中的多级生物学障碍而很难将两种药物同时运载至肿瘤组织。本项目设计合成多功能化化疗药物和基因药物共载体系，用于联合抗肿瘤治疗。该共载体系具有如下特点：（1）利用可生物降解的多臂接枝聚合物MP-g-OEI担载siRNA形成的阳离子纳米复合物作为内核；（2）合成键合有化疗前药Pt（IV）的多功能化可电荷翻转的聚合物作为遮蔽体系。调控遮蔽体系的组成，使共载体系在体内传递过程中带负电，到达肿瘤组织带正电，提高协同抗肿瘤作用；（3）低毒的Pt（IV）药进入肿瘤细胞后，在还原环境中被还原为高抗癌活性的Pt（II）药，杀伤肿瘤细胞。本项目通过实验明确共载体系各个单元在传递过程的行为，了解化疗药物与siRNA协同作用机理，以及通过改变各单元的配比、装配方法来提高对肿瘤的治疗效果。

化疗药物和基因药物相结合是治疗肿瘤的有效方式，在癌症治疗领域获得了高度重视。传统的药物载体无法有效克服体内传输过程中的多级生物学障碍将两种药物同时运载至肿瘤组织。本项目设计合成多功能化化疗药物和基因药物共载体系，用于联合抗肿瘤治疗。该共载体系具有如下特点：（1）利用可生物降解的多臂接枝聚合物MP-g-OEI担载基因物质形成的阳离子纳米复合物作为内核。（2）合成多功能化的可电荷翻转的聚合物作为遮蔽体系。调控遮蔽体系的组成，使共载体系在体内传递过程中带负电，到达肿瘤组织带正电，提高协同抗肿瘤作用。（3）通过基因治疗作用，改变了肿瘤细胞的相关基因，从而促进了化疗药物杀伤肿瘤细胞的效果。本项目通过实验明确共载体系各个单元在传递过程的行为，了解化疗药物与基因药物协同作用机理，以及通过改变各单元的配比、装配方法来提高对肿瘤的治疗效果。