Cascade Mesophase Transitions of Multi-enzyme Responsive Polymeric Formulations

Parul Rathee, Nicole Edelstein-Pardo, Gil Koren, Roy Beck, Roey J. Amir*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Studying how synthetic polymer assemblies respond to sequential enzymatic stimuli can uncover intricate interactions in biological systems. Using amidase- and esterase-responsive PEG-based diblock (DBA) and triblock amphiphiles (TBAs), we created two distinct formulations: amidase-responsive DBA with esterase-responsive TBA and vice versa. We studied their cascade responses to the two enzymes and the sequence of their introduction. These formulations underwent cascade mesophase transitions upon the addition of the DBA-degrading enzyme, transitioning from (i) coassembled micelles to (ii) triblock-based hydrogel, and ultimately to (iii) dissolved polymers when exposed to the TBA hydrolyzing enzyme. The specific pathway of the two mesophase transitions depended on the compositions of the formulations and the enzyme introduction sequence. The results highlight the potential for designing polymeric formulations with programmable multistep enzymatic responses, mimicking the complex behavior of biological macromolecules.

Original languageEnglish
Pages (from-to)3607-3619
Number of pages13
Issue number6
StatePublished - 10 Jun 2024


FundersFunder number
Tel Aviv University
Israel Science Foundation1454/20, 413/22
Israel Science Foundation


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