Protein-responsive protein release of supramolecular/polymer hydrogel composite integrating enzyme activation systems

Hajime Shigemitsu, Ryou Kubota, Keisuke Nakamura, Tomonobu Matsuzaki, Saori Minami, Takuma Aoyama, Kenji Urayama and Itaru Hamachi ()
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Hajime Shigemitsu: Graduate School of Engineering, Kyoto University, Nishikyo-ku
Ryou Kubota: Graduate School of Engineering, Kyoto University, Nishikyo-ku
Keisuke Nakamura: Graduate School of Engineering, Kyoto University, Nishikyo-ku
Tomonobu Matsuzaki: Graduate School of Engineering, Kyoto University, Nishikyo-ku
Saori Minami: Kyoto Institute of Technology
Takuma Aoyama: Kyoto Institute of Technology
Kenji Urayama: Kyoto Institute of Technology
Itaru Hamachi: Graduate School of Engineering, Kyoto University, Nishikyo-ku

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Non-enzymatic proteins including antibodies function as biomarkers and are used as biopharmaceuticals in several diseases. Protein-responsive soft materials capable of the controlled release of drugs and proteins have potential for use in next-generation diagnosis and therapies. Here, we describe a supramolecular/agarose hydrogel composite that can release a protein in response to a non-enzymatic protein. A non-enzymatic protein-responsive system is developed by hybridization of an enzyme-sensitive supramolecular hydrogel with a protein-triggered enzyme activation set. In situ imaging shows that the supramolecular/agarose hydrogel composite consists of orthogonal domains of supramolecular fibers and agarose, which play distinct roles in protein entrapment and mechanical stiffness, respectively. Integrating the enzyme activation set with the composite allows for controlled release of the embedded RNase in response to an antibody. Such composite hydrogels would be promising as a matrix embedded in a body, which can autonomously release biopharmaceuticals by sensing biomarker proteins.

Date: 2020
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DOI: 10.1038/s41467-020-17698-0

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