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.