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

• Published in: Mikrochimica acta (1966) 2024-08, Vol.191 (8), p.447
• Main Authors: Wei, Fenghuang, Hou, Li, Yao, Yiyun, Lai, Yunping, Lin, Tianran, Zhao, Shulin, Tang, Dianping
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Animals; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cascade chemical reactions; Cell Line, Tumor; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Copper; Copper - chemistry; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Delivery Systems; Drug Liberation; Gluconic acid; Glucose oxidase; Glucose Oxidase - chemistry; Glucose Oxidase - metabolism; Glutathione; Humans; Hyaluronic acid; Hyaluronic Acid - chemistry; Hydrogen peroxide; Hydrogen Peroxide - chemistry; Hydrogen Peroxide - metabolism; Hydroxyl radicals; Imidazoles; Loading rate; Metal-Organic Frameworks - chemistry; Mice; Microengineering; Nanochemistry; Nanotechnology; Neoplasms - drug therapy; Original Paper; Tumor Microenvironment - drug effects; Tumors; Zeolites - chemistry
• ISSN: 0026-3672; 1436-5073; 1436-5073
• DOI: 10.1007/s00604-024-06527-6

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 2+ in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce H 2 O 2 and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu 2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu + . The generated Cu + and H 2 O 2 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%). Graphical abstract