Nanotechnology Reviews (Apr 2022)

Glucose-responsive nanogels efficiently maintain the stability and activity of therapeutic enzymes

  • Qi Hongzhao,
  • Yang Jie,
  • Yu Jie,
  • Yang Lijun,
  • Shan Peipei,
  • Zhu Sujie,
  • Wang Yin,
  • Li Peifeng,
  • Wang Kun,
  • Zhou Qihui

DOI
https://doi.org/10.1515/ntrev-2022-0095
Journal volume & issue
Vol. 11, no. 1
pp. 1511 – 1524

Abstract

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To date, the encapsulation of therapeutic enzymes in a protective matrix is an optimized strategy for the maintenance of their stability, facilitating their clinical application. However, the stability and activity of therapeutic enzymes are often in tension with each other. A rigid protective matrix may effectively maintain the stability of therapeutic enzymes, but it can reduce the diffusion of substrates toward the therapeutic enzyme active site, dramatically affecting their catalytic efficiency. Here, we exploited a kind of nanogels by in situ polymerization on the arginine deiminase (ADI) surface with 3-acrylamido-phenylboronic acid (APBA) monomer. These nanogels efficiently improved the thermal stability (25–75℃), the pH stability (pH 1–13), and protease (trypsin) stability of ADI due to the strong rigidity of the surface poly(APBA) shell. And even after 60 days of storage, ∼60% of the activity of ADI encapsulated by nanogels remained. Furthermore, ADI encapsulated by nanogels could efficiently degrade arginine to increase the ratio of citrulline to arginine in mice plasma. That is because autologous glucose binds with APBA leading to the hydrophilicity increase of nanogels, and then, the arginine molecules can readily diffuse toward the encapsulated ADI. This nanogel platform eases the tension between the stability and activity of therapeutic enzymes. The resulting nanogels can efficiently maintain the in vitro stability and the in vivo activity of therapeutic enzymes, facilitating the exploitation of new therapeutic enzyme formulations, which can be transported and stored in vitro for a long time and be applied effectively in vivo.

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