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

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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

DOI 10.1002/adfm.201707371

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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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Authors: Zhu, Q., Chen, X., Xu, X., Zhang, Y., Zhang, C., & Mo, R.
Affiliations: China Pharmaceutical University (CN)
Corresponding author: Mo, Ran
ORCID: Zhu, Qiuwen
Chen, Xiaojie
Xu, Xiao
Zhang, Can
Mo, Ran
Venue: Advanced Functional Materials
Publisher: Wiley
Published: 2018-02-19
Volume: 28
Issue: 17
ISSN: 1616-301X (ISSN-L)
1616-3028
DOI: 10.1002/adfm.201707371
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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: Physical Sciences › Materials Science › Biomaterials › 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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Tumor‐Specific Self‐Degradable Nanogels as Potential Carriers for Systemic Delivery of Anticancer Proteins

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