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《Chinese Science Bulletin》 2018-12
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Enzyme-catalysed in vivo self-assembly?

Xiaoxiao Zhao;Lili Li;Hao Wang;CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology (NCNST);Sino-Danish College, University of Chinese Academy of Sciences;  
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.
【Fund】: 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
【CateGory Index】: TQ460.1
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