The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Tumor‐Specific Self‐Degradable Nanogels as Potential Carriers for Systemic Delivery of Anticancer Proteins
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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“HA is known to target the overly expressed CD44 receptors in several tumors including MDA-MB-231 human breast cancer 41 and A549 lung cancer.42,43”
From Catalase-Integrated Hyaluronic Acid as Nanocarriers for Enhanced Photodynamic Therapy in Solid Tumor (2019) · cites this paper as [43]
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Metadata
- 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
- 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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