为什么要设计酶催化活体自组装?

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.