Issue 36, 2024

A self-assembled copper-artemisinin nanoprodrug as an efficient reactive oxygen species amplified cascade system for cancer treatment

Abstract

Chemodynamic therapy (CDT) is a tumor-specific intervention methodology, which is based on the upregulation of reactive oxygen species (ROS) content by triggering the Fenton or Fenton-like reaction within the tumor microenvironment (TME). However, there are still challenges in achieving high-efficiency CDT on account of both the limited intracellular hydrogen peroxide (H2O2) and delivery efficiency of Fenton metal ions. Copper-based nanotherapeutic systems have attracted extensive attention and have been widely applied in the construction of nanotherapeutic systems and multimodal synergistic therapy. Herein, we propose a strategy to synergize chemotherapy drugs that upregulate intracellular ROS content with chemodynamic therapy and construct an artemisinin-copper nanoprodrug for proof-of-concept. With the proposed biomimetic self-assembly strategy, we successfully construct an injectable nanoprodrug with suitable size distribution and high drug loading content (68.1 wt%) through the self-assembly of amphiphilic artemisinin prodrug and copper ions. After reaching the TME, both Cu2+ ions and free AH drugs can be released from AHCu nanoprodrugs. Subsequently, the disassembled Cu2+ ions are converted into Cu+ ions by consuming the intracellular GSH. The generated Cu+ ions serve as a highly efficient Fenton-like reagent for robust ROS generation from both AH and tumor-over-produced H2O2. Results show that the nanoprodrug can realize the cascade amplification of ROS generation via artemisinin delivery and subsequent in situ Fenton-like reaction and a high tumor inhibition rate of 62.48% in vivo. This work provides a promising strategy for the design and development of an efficient nanoprodrug for tumor-specific treatment.

Graphical abstract: A self-assembled copper-artemisinin nanoprodrug as an efficient reactive oxygen species amplified cascade system for cancer treatment

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Article information

Article type
Communication
Submitted
06 Jun 2024
Accepted
22 Aug 2024
First published
23 Aug 2024

J. Mater. Chem. B, 2024,12, 8902-8910

A self-assembled copper-artemisinin nanoprodrug as an efficient reactive oxygen species amplified cascade system for cancer treatment

X. Zhu, C. Bi, W. Cao, S. Li, C. Yuan, P. Xu, D. Wang, Q. Chen and L. Zhang, J. Mater. Chem. B, 2024, 12, 8902 DOI: 10.1039/D4TB01237B

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