摘要
自组装纳米材料在药物递送方面的应用具有巨大的潜能.其尺寸的可调控性、病理环境响应性等物理化学行为,使得自组装纳米载体可以通过改进主动靶向、被动靶向、血液长循环等方面来提高药物递送能力.然而,相对于大量基础研究的投入,目前的临床转化依然面临着巨大的挑战.其中除了药物研发固有的高风险特征外,其主要原因还包括自组装纳米材料在体的稳定性、递送效率以及代谢毒性等问题.由此,我们从自然的自组装过程中得到启发,率先发展了活体自组装(in vivo self-assembly)的策略.它是指通过将外源性的分子引入到特定的生理和病理环境下,在细胞、组织甚至活体生物内进行自组装,形成可控的高级有序结构.通过调控其在复杂生物环境下时空可控的组装,从而实现特定的功能.体内自组装纳米药物具有组装诱导滞留(assembly induced retention,AIR)效应,能够显著增强药物在靶点病灶部位的富集和滞留,增强递送效率,提高药物利用率,同时降低药物在肝肾部位的蓄积,降低了毒性副作用,为癌症等重大疾病的诊断和治疗提供了新思路和新策略.
Traditional strategy for specific drug delivering is by constructing a responsive nanocarrier,which prove to effective in increasing drug efficiency and decreasing side effects.Various research can improve delivery efficiency by introducing active targeting,passive targeting and long-term circulation motif to molecular design.Whereas,impute efforts do not correlate with clinical transform.Researchers are enlightened by self-assembly process in nature,which is happening all the time and all the where,and plays both positive and negative roles in the body.Self-assembly tells that many components will aggregate into specific pattern or structure without other intervening forces.Herein,our strategy is going to construct in vivo self-assembly,by instructing molecules to self-assembly into highly-ordered structures under specific biological and pathological sites in terms of cells,tissues and even animals.These assemblies show higher accumulation and longer retention in-situ.Therefore,it is promising to achieve enhanced theranostic effect.Enzyme is a widely spread and specific catalyst,it is promising to manipulate enzyme triggered peptide self-assembly in specific disease site.Peptide self-assembly have been widely researched.Phenylalanine and diphenylalanine are reported minimum self-assembled amino acid and dipeptides.Some self-assembled short peptides and their derivative are rich in aromatic group,e.g.,Fmoc-Phe-Arg,Cys-Phe-Phe.Some phosphorylated short peptides are hydrophilic,which would turn into hydrophobic and then self-assemble into hydrogel after phosphatase cleavaging phosphate group.Peptide amphiphiles can self-assembled into multi-morphologies and have showed widespread application in regenerative medicine,which also showed enzymatic-controllable self-assembly.Polypeptides,peptide-polymer complexes and nature-derived peptides are also applicable for constructing self-assemble system.Some enzymes are overexpressed in disease site,so we can design enzyme triggered self-assembly,therefore increasing imaging sensitivity and efficiency of chemotherapy,and also showed decreased toxicity duo to biocompatible peptides used.In a word,in vivo self-assembly is of great potential to explore its application in disease theranostics.
作者
赵小小
李莉莉
王浩
Xiaoxiao Zhao;Lili Li;Hao Wang(CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoseience, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China;Sino-Danish College, University of Chinese Academy of Sciences, Beijing 100049, China)
出处
《科学通报》
EI
CAS
CSCD
北大核心
2018年第12期1088-1094,共7页
Chinese Science Bulletin
基金
国家杰出青年科学基金(51725302)
国家自然科学基金创新研究群体项目(11621505)
国家自然科学基金(51573032,31671028)
中国科学院青年创新促进会(2017053)资助
关键词
活体自组装
酶催化
多肽
长效滞留
in vivo self-assembly
enzyme catalyzed
peptides
long-term retention