A drug ligand based bimetallic coordination-driven self-assembly nanodrug for high-efficiency tumor chemodynamic therapy

• Published in: Materials today chemistry 2024-03, Vol.36, p.101977, Article 101977
• Main Authors: Zhu, Yin-Yin, Huang, Cheng-Jie, Zhong, Hao, Shi, Qun-Ying, Lai, Jin-Mei, Liu, Jun-Han, Liu, Li-Han
• Format: Article
• Language: English
• Subjects: Chemodynamic therapy; Coordination-driven self-assembly; GSH depletion; Ions interference; Tumor therapy
• ISSN: 2468-5194; 2468-5194
• DOI: 10.1016/j.mtchem.2024.101977

Low chemodynamic catalytic efficiency at weakly acidic microenvironment, inadequate H2O2 and high glutathione (GSH) levels in tumor cells severely limit the efficacy of chemodynamic therapy (CDT). To address these problems, a bimetallic coordination-driven self-assembly nanoparticle named AZC@HA NP is fabricated using the catalase inhibitor 3-amino-1, 2, 4-triazole (3-AT) as the coordination ligands of both copper (II) and zinc (II) ions. Interestingly, parts of Cu2+ converted into Cu+ after coordination. Cu+ ions in AZC@HA NPs catalyze the Fenton-like reaction at weakly acidic and neutral microenvironment to produce •OH for CDT. 3-AT elevates intracellular H2O2 level thus augments the •OH generation by inactivating the catalase. AZC@HA NPs decrease intracellular GSH level thus reduce the resistance of tumor cells to CDT through both Cu2+-mediated GSH depletion and “Zn2+ interference” mediated GSH synthesis suppression. Surface coating of hyaluronic acid (HA) allow the targeted accumulation of AZC@HA NPs on CD44 overexpressed tumor cells. The AZC@HA NPs show significantly enhanced tumor inhibition in vitro and in vivo. Overall, the as-prepared tumor targeting, H2O2 elevating and dual GSH exhausting coordination-driven self-assembly nanodrugs AZC@HA NPs provide an innovative strategy for high efficient CDT. A drug ligand based bimetallic coordination-driven self-assembly nanodrug named AZC@HA is fabricated to enhance efficiency of chemodynamic therapy by catalase inhibition mediated H2O2 saving and “Zn2+ interference” accelerated GSH depletion. [Display omitted] •A drug ligand based bimetallic nanodrug AZC@HA NPs was constructed by the coordination-driven self-assembly of 3-AT with both Zn2+ and Cu2+ for high-efficiency CDT.•The AZC@HA NPs amplified Fenton-like catalytic reaction-mediated oxidative stress through simultaneously 3-AT-mediated H2O2 saving, Cu+-mediated ROS generation, Zn2+-mediated GSH synthesis inhibition and Cu2+-triggered GSH elimination.•AZC@HA NP is almost entirely composed of therapeutic components, possessing high drug loading efficacy and good biosafety.