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.

Collaborative assembly-mediated siRNA delivery for relieving inflammation-induced insulin resistance

“…S1 in the Electronic Supplementary Material (ESM)), which are used for chemical crosslinking mediated by radical polymerization and functional modification of PEG and ligands, respectively. The degree of modification of methacrylic groups was calculated to be ~25% based on the 1 H nuclear magnetic resonance (NMR) spectrum [47], while that of thiol groups was determined to be ~ 3% using the Ellman method [48]. The binary complex of siRNA/protamine could pack siRNA, as confirmed by no visible free siRNA band using the agarose gel electrophoretic imaging ( Fig.…”

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