生物医用纳米材料在增强肿瘤细胞免疫原性死亡中的应用  

Biomedical nanomaterials for the enhancement of immunogenic cell death-based cancer immunotherapy

作　　者：庞小雨 董岸杰[1] 邓联东[1] 程亚亚 邓宏章 Xiaoyu Pang;Anjie Dong;Liandong Deng;Yaya Cheng;Hongzhang Deng(School of Chemical Engineering and Technology,Tianjin University,Tianjin 300350,China;School of Life Science and Technology,Xidian University,Xi'an 710126,China)

机构地区：[1]天津大学化工学院,天津300350 [2]西安电子科技大学生命科学技术学院,西安710126

出　　处：《科学通报》2022年第13期1436-1448,共13页Chinese Science Bulletin

基　　金：国家自然科学基金(32171320,82102213)资助。

摘　　要：激活机体的适应性免疫反应是提升长期抗肿瘤疗效的关键因素.化学治疗、放射治疗、光动力治疗(photodynamic therapy,PDT)等方法可诱导肿瘤细胞发生凋亡并伴随着免疫原性死亡(immunogenic cell death,ICD).ICD引起的损伤相关分子模式(damage associated molecular patterns,DAMPs)分子的暴露或释放可刺激免疫系统发挥抗肿瘤免疫作用,招募抗原递呈细胞(antigen-presenting cell,APC),激活T细胞适应性免疫应答.因此,在肿瘤免疫治疗中ICD诱导剂可以改善其治疗效果,从而提高患者生存率.越来越多的研究表明,基于纳米材料的癌症治疗平台不仅可以实现特定肿瘤微环境(tumor microenvironment,TME)刺激响应的药物控制释放,并且其可以调节TME进而诱导肿瘤细胞发生ICD,这撞击出了癌症纳米医学的新火花.自此以后,设计和构建增强肿瘤ICD效应的生物医用材料的相关研究受到了极大关注.基于此背景,本文首先介绍了肿瘤ICD的成因以及纳米材料在诱导肿瘤ICD中发挥的多重功能.其次,阐述了纳米材料在调控TME,改善肿瘤治疗效果方面所具有的巨大潜力.最后,对纳米材料在诱导肿瘤ICD研究中所面临的挑战也进行了展望性的深入探讨.The activation of adaptive antitumor immune response is paramount for improving the long-term antitumor efficiency.Chemotherapy,radiotherapy,and photodynamic therapy(PDT)can induce cell apoptosis and immunogenic cell death(ICD).Subsequently,the exposure or release of damage-associated molecular patterns(DAMPs)caused by ICD can stimulate the immune system to exert an antitumor immune response,recruit the antigen-presenting cells,and activate the adaptive immune responses of T cells.As such,the application of ICD inducers in tumor therapy is of crucial role in improving the therapeutic effects and the survival rate of cancer patients.Recently,accumulating evidence has revealed that nanomaterials-based platforms for cancer treatment could not only achieve controlled drug release in response to stimulation of tumor microenvironment(TME),but also regulate TME to enhance ICD in the tumor.Hence,the construction of ICD effects-based biomedical nanomaterials has sparked tremendous attention.Benefiting from their unique size,biomedical nanomaterials are commonly applied as ICD inducers carriers to target tumor tissue and enhance selective enrichment in the tumor.By taking advantage of their easily modified surface properties and multi-selectivity of raw materials,nanomaterials can also be designed as functionalized carriers with stimulus responses to TME,thereby achieving stepwise and controlled release of ICD inducers.Meanwhile,biomedical nanomaterials are capable of codelivering different components,protecting the payload from degradation and precise controlled release.These abilities enable nanomaterials to amplify the antitumor effects of chemotherapy,radiotherapy,PDT and many other emerging therapies.Of note,a single therapy has been limited by many factors.Chemotherapy and radiotherapy can bring about irreversible damage to normal tissue cells and immune cells.The hypoxic TME limits the function of PDT.On top of that,monotherapy has been also vulnerable to tumor heterogeneity.On this ground,combination therapy has be

关 键 词：纳米材料 免疫原性死亡 药物递送 免疫治疗 联合治疗 

分 类 号：R730.51[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]