An intelligent Cu/ZIF-8-based nanodrug delivery system for tumor-specific and synergistic therapy via tumor microenvironment-responsive cascade reaction.

Mikrochim Acta

Key Laboratory for Analytical Science of Food Safety and Biology (MOE & Fujian Province), Department of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China.

Published: July 2024

An intelligent nanodrug delivery system (Cu/ZIF-8@GOx-DOX@HA, hereafter CZGDH) consisting of Cu-doped zeolite imidazolate framework-8 (Cu/ZIF-8, hereafter CZ), glucose oxidase (GOx), doxorubicin (DOX), and hyaluronic acid (HA) was established for targeted drug delivery and synergistic therapy of tumors. The CZGDH specifically entered tumor cells through the targeting effect of HA and exhibited acidity-triggered biodegradation for subsequent release of GOx, DOX, and Cu in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce HO and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu. The generated Cu and HO triggered the Fenton-like reaction to generate toxic hydroxyl radicals (·OH), which disrupted the redox balance of tumor cells and effectively killed tumor cells for chemodynamic therapy (CDT). Therefore, synergistic multimodal tumor treatment via TME-activated cascade reaction was achieved. The nanodrug delivery system has a high drug loading rate (48.3 wt%), and the three-mode synergistic therapy has a strong killing effect on tumor cells (67.45%).

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http://dx.doi.org/10.1007/s00604-024-06527-6DOI Listing

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