pH响应活体自组装生物材料及其在肿瘤诊疗中的应用进展  

pH-responsive in vivo self-assembled biomaterials and their application for tumor diagnosis and therapy

作　　者：郑蕊 安红维[1,2] 王浩 Rui Zheng;Hongwei An;Hao Wang(Key Laboratory for Biomedical Effects of Nanomaterials &Nanosafety,Center for Excellence in Nanoscience,Chinese Academy of Sciences, National Center for Nanoscience and Technology,Beijing 100190,China;School of Nanoscience and Technology,University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]国家纳米科学中心,中国科学院纳米生物效应与安全性重点实验室,中国科学院纳米科学卓越创新中心,北京100190 [2]中国科学院大学纳米科学与技术学院,北京100049

出　　处：《科学通报》2018年第35期3799-3807,共9页Chinese Science Bulletin

基　　金：国家杰出青年科学基金(51725302)资助.

摘　　要：自组装纳米材料在肿瘤部位具有被动靶向富集效应,提高了药物的递送能力,在生物医学领域具有广阔的发展前景.然而,本质上处于动态平衡的自组装纳米材料在体内传送时会与各种生物界面或生物大分子相互作用,存在结构不稳定的问题,目前还难以实现对其结构的精准控制,这妨碍了它们的进一步临床应用.pH会影响氨基酸的电荷状态,从而对多肽自组装过程中的静电相互作用造成影响,因此改变pH是调控多肽自组装过程的常用方法之一.在此,我们基于活体自组装(invivoself-assembly)的理念,着重综述了基于pH响应型多肽的纳米生物材料的原位制备方法并探讨了其在肿瘤诊断和治疗中的应用研究.通过把用于肿瘤诊疗的功能分子与pH响应型多肽结合,可以构建更复杂的具有生物功能的组装体系,提高成像剂的诊断功能和化疗药物的治疗效果.因此,利用pH响应型多肽在活体中原位构建有序组装体的新策略为开发肿瘤诊疗的纳米材料铺平了道路,为推向临床应用带来了新希望.The passive targeting of self-assembled nanomatefials at tumor sites can improve drug delivery capability,which has great prospects in biomedical field.However,dynamically balanced self-assembled nanomaterials will interact with a variety of biological interfaces or biological macromolecules in vivo,and there are problems with structural instability, and it is difficult to achieve accurate control of their structure,which hampers their further clinical application. pH can affect the electrical charge of the amino acids,which affects the electrostatic interaction of polypeptides in the process of self-assembly,so changing the pH is one of the ways to regulate the process of self-assembly.In this way,we propose in vivo self-assembly strategy based on the pH-response peptide for tumor diagnosis and therapy.After reaching the tumor sites,the exogenous molecules structure will change under the stimulus of the acidic tumor microenvironment, and then form a highly ordered nanostructure,which can prolong the retention time of the material and improve the utilization effect.Starting from the design of small molecular peptides,polypeptides are combined with other functional biomolecules,and pH change at tumor sites is used to construct pH-responsive in vivo self-assembled materials.In this way,accurate and controllable diagnosis and therapy can be realized. The acidic tumor microenvironment is one of the most prominent characteristics of tumor microenvironment and is a good trigger for designing microenvironmental responsive molecules.Our group designed a pH-sensitive molecule BP-KLVFF-His6-PEG,the hydrophilic and hydrophobic balance was destroyed after reaching the acidic environment at the tumor site (pH 6.5).Driven by the hydrogen bonds of the KLVFF fragment,the molecule was self-assembled to form nanofibers.Combined with the imaging agent Nero red and doxorubicin,it can be used for long-term tumor imaging and enhancement to therapeutic efficacy.By combining functional molecules of tumor diagnosis and therapy with pH-re

关 键 词：活体自组装 生物纳米材料 PH响应 多肽 诊断治疗 

分 类 号：R318.08[医药卫生—生物医学工程]