Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 20, Pages 22492-22498Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c02572
Keywords
enzymatic-instructed self-assembly; preorganization; peptides; antitumor; nanomedicine
Funding
- National Natural Science Foundation of China [51973096, 51773097, 31900998, 51703097]
- National Program for Support of Top-Notch Young Professionals [31825012]
- Young Elite Scientists Sponsorship Program by Tianjin [TJSQNTJ-2017-16]
- Tianjin MSTC [15JCZDJC38100, 18JCQNJC04000]
- China Postdoctoral Science Foundation [2017M612802]
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Inspired by the biological process of phosphorylation for which different sites of the same protein may have different activities and functions, we utilized phosphatase-based enzyme-instructed self-assembly (EISA) to construct self-assembled nanomedicine from the precursors with different phosphorylated sites. We found that, although the obtained self-assembling molecules after EISA were identical, the changes of EISA catalytic sites could determine the outcome of molecular self-assembly. The precursor with the phosphorylated site in the middle preorganized before EISA, while the ones with other phosphorylated sites could not preorganize before EISA. After EISA, the preorganized precursor then resulted in more stable and ordered assemblies than those of the others, which showed increased cellular uptake and up to 1.7-fold higher efficacy in an antitumor therapeutic compared to those assembled from unorganized precursors.
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