Cited by 105Hydrogels: synthesis, properties, applicationsNanoparticle-Based Drug DeliveryDendrimers and Hyperbranched Polymers

Tumor‐Specific Self‐Degradable Nanogels as Potential Carriers for Systemic Delivery of Anticancer Proteins

Zhu, Qiuwen, Chen, Xiaojie, Xu, Xiao, Zhang, Ying, Zhang, Can, Mo, Ran·2018·Advanced Functional Materials

Abstract

Development of a safe and effective carrier for systemic protein delivery is highly desirable, which depends on management of the relationship among loading capacity, stability, delivery efficiency, and degradability. Here, a tumor‐specific self‐degradable nanogel composed of hyaluronidase (HAase)‐degradable hyaluronic acid (HA) matrices entrapping acid‐activatable HAase (aHAase) for systemic delivery of anticancer proteins is reported. Collaboratively crosslinked nanogels (cNG) obtained by the synthetic cholesteryl methacrylated HA show high protein‐loading capacity and stability. The aHAase is engineered by modifying the HAase with citraconic anhydride to shield its HA‐degrading activity, which can be reversibly activated by hydrolysis of the citraconic amide under acidic condition. In the tumor microenvironment, the mild acidity activates the aHAase partially, which results in swelling of the cNG and releasing of the aHAase. The released reactivated aHAase can degrade the HA that is also a major constituent of tumor extracellular matrix to increase perfusion of the cNG in the tumor stroma. In the acidic endocytic vesicles, the aHAase is fully reactivated. The active aHAase completely degrades the cNG to release the encapsulated anticancer protein, deoxyribonuclease I intracellularly, which digests the DNA to cause tumor cell death for enhanced antitumor efficacy.

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Crossref · 10.1002/adfm.201707371

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Authors
Zhu, Q., Chen, X., Xu, X., Zhang, Y., Zhang, C., & Mo, R.
Affiliations
China Pharmaceutical University (CN)
Corresponding author
Mo, Ran
Venue
Advanced Functional Materials
Publisher
Wiley
Published
2018-02-19
Volume
28
Issue
17
ISSN
  • 1616-301X (ISSN-L)
  • 1616-3028
OpenAlex
W2793437963
Cited by
105
References
67
Citations by year
2026: 1 · 2025: 4 · 2024: 4 · 2023: 14 · 2022: 11 · 2021: 17 · 2020: 19 · 2019: 22 · 2018: 13
FWCI
6.70
Type
journal article
Language
en
Open access
closed
Locations
Advanced Functional Materials (publishedVersion)
Funders
  • National Natural Science Foundation of China (81673381)
  • Natural Science Foundation of Jiangsu Province
  • China Association for Science and Technology (2015QNRC001)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
hyaluronic acid, hyaluronidase, tumor-specific drug delivery, anticancer proteins, DNase I, citraconic anhydride, tumor acidosis, tumor extracellular matrix, endocytic vesicles, protein loading capacity

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