可激活肿瘤细胞Fas-FasL凋亡通路的免疫纳米药物的制备及抗肿瘤效果研究

项目名称： 可激活肿瘤细胞Fas-FasL凋亡通路的免疫纳米药物的制备及抗肿瘤效果研究

项目编号： No.21474047

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 胡勇

作者单位： 南京大学

项目金额： 88万元

中文摘要： 传统的肿瘤免疫疗法，需采用复杂、费时的基因工程、抗体技术，适用面窄；而单独注射抗体，又会引起生物体的免疫性疾病。本项目采用表面工程化技术及肿瘤信号分子响应技术，构建多层次，程序性发挥生理功能的免疫纳米药物，用于肿瘤的免疫治疗。将单克隆凋亡抗体anti-CD95（MAB95）修饰在免疫纳米药物表面，当其被输送到肿瘤组织，受肿瘤组织高表达的MMP-2分子激发，离去外层的PEG保护层，露出表面的MAB95，激活肿瘤细胞的Fas-FasL凋亡通道，无需进入细胞，即可介导肿瘤细胞的凋亡，不会引起肿瘤细胞的多药耐受性，有效的克服了上述缺点。此外，当外层的PEG层在肿瘤组织表面脱落后，免疫纳米药物的粒径变小，有助于免疫纳米药物通过组织间隙，从肿瘤血管或肿瘤组织边缘进入肿瘤组织内部，增强抗肿瘤效果。这一体系将靶向纳米药物和免疫治疗技术有机结合起来，为恶性肿瘤的治疗提供新思路。

中文关键词： 生物材料；生物医用高分子；纳米药物；免疫治疗；纳米颗粒

英文摘要： In this project, a multi-layer immuno nanomedicine, conjugated with the monoclonal antibody: anti-CD95(MAB95), will be constucted through surface engineering technology. This nanomedicine can respond to the MMP-2, which is highly expressed by the tumor, release the PEG layer and expose the MAB95 to the tumor cells, thus inducing the apoptosis of tumor cells through re-openning the Fas-FasL apoptosis pathway, showing excellent anti-tumor effect. Compared to the traditional immuno therapy methods, this system is simple and avoilds the time assuming steps of gene engineering. This nanomedicine will not induce multi-drug resistence, because it do not need enter into the the tumor cells to show the anti-tumor effect. Besides, after the detachment of the outside layer of PEG, the size of the immuno nanomedicine will become smaller, which partly breaks up the biological barrier of tumor tissue and improves the penetration of this nanomedicine into the nearby tumor tissue, increasing the anti-tumor therapeutic effect. This immune nanomedicine integrates the nano drug delivery system and immune therapy technology, which will open a new window on the treatment of tumor.

英文关键词： biomaterials;biomedical polymer;nanomedicine;immuno therapy;nanoparticles