Copper-Cysteamine Nanoparticles as a Heterogeneous Fenton-Like Catalyst for Highly Selective Cancer Treatment

Herein, for the first time, we report copper-cysteamine (Cu-Cy) nanoparticles having Cu¹⁺ instead of Cu²⁺ as an efficient heterogeneous Fenton-like catalyst for highly selective cancer treatment. Initial measurements of Cu-Cy's hydroxyl radical generation ability show that it behaves as a Fenton-like reagent in the presence of H₂O₂ (100 μM) at pH 7.4, and that its Fenton-like activity is dramatically enhanced under acidic conditions (pH 6.5 and 5.5). Notably, Cu-Cy exhibits high stability and minimal copper release during the Fenton-like reaction, demonstrating its potency as a heterogeneous Fenton-like catalyst with a low cytotoxic effect. Through extensive in vitro studies, Cu-Cy NPs are found to generate a significantly higher level of ROS, thereby causing significantly more destruction to cancerous cells than to normal cells without the need for exogenous additives, such as H₂O₂. To the best of our knowledge, the average IC-50 value of Cu-Cy to cancer cells (11 μg/mL) is the lowest among reported heterogeneous Fenton-like nanocatalyst so far. Additionally, compared to cancer cells, Cu-Cy NPs display substantially higher IC-50 value toward normal cells (50 μg/mL), suggesting high selectivity. Overall, Cu-Cy NPs can participate in heterogeneous Fenton-like activity with elevated H₂O₂ under acidic conditions to produce significantly higher levels of hydroxyl radicals in cancer cells when compared to normal cells, resulting in selective cytotoxicity to cancer cells.