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Atom-precise fluorescent copper cluster for tumor microenvironment targeting and transient chemodynamic cancer
Zhenzhen Yang1, Anli Yang2, Wang Ma1
1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Background:
Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limit the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment.
Results:
In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner.
Conclusions:
This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level.
Insights
Atomically precise copper nanoclusters (Cu6NC) offer a novel approach to cancer therapy by generating reactive oxygen species (ROS) in acidic tumor environments. This targeted chemodynamic therapy demonstrates high efficacy against cancer cells with minimal harm to healthy tissues.
Area of Science:
- Nanotechnology
- Materials Science
- Biomedical Engineering
Background:
- Reactive oxygen species (ROS) are explored for cancer therapy but face challenges with instability and off-target damage.
- Metal nanoclusters (NCs) with precise structures are investigated for targeted ROS release, yet few effectively target the tumor microenvironment.
Purpose of the Study:
- To develop an atomically precise nanocluster for targeted reactive oxygen species (ROS) generation in the tumor microenvironment.
- To evaluate the chemodynamic anti-tumor properties and biological safety of the developed nanocluster.
Main Methods:
- Synthesis of an atomically precise nanocluster, Cu6(C4H3N2S)6 (Cu6NC).
- Investigation of Cu6NC's ROS generation triggered by acidic conditions.
- Assessment of Cu6NC's cytotoxicity in vitro and in vivo against normal and tumor cells.
Main Results:
- Cu6NC demonstrated slow ROS generation in acidic environments, indicating targeted release.
- The nanocluster exhibited high biological safety and efficient chemodynamic anti-tumor properties.
- In vitro and in vivo studies confirmed low cytotoxicity to normal cells and high, concentration-dependent cytotoxicity to tumor cells.
Conclusions:
- Cu6NC represents a promising candidate for chemodynamic cancer therapy.
- This work provides a new atomic-level strategy to address clinical challenges in cancer treatment.
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