Engineering a self-fueling and self-reported theranostic nanocatalyst for amplified cancer imaging and chemodynamic therapy

Abstract

Chemodynamic therapy (CDT) has sparked increasing interest in selective cancer treatment. However, it remains a challenge to achieve an efficient and sustained therapeutic effect due to the restricted Fenton chemistry and deficient catalytic substrates within the tumor microenvironment (TME). Meanwhile, the lack of strategies to timely monitor the delivery and execution of CDT agents increases the risks of unwanted side effects. Here, we present that integration of TME-triggered cascade catalysis with tumor metabolism reprogramming to engineer activatable theranostic nanocatalysts is an effective way to tackle these challenges. A self-fueling and self-reported theranostic nanocatalyst is reported in this study by modifying multi-enzyme mimic MnO2 nanosturctures with antisense oligonucleotides (ASO). This catalyst can produce free radicals through logic multi-enzymatic catalysis to induce oxidative damage to cancer cells, yet keeping inert in normal cells. Furthermore, the loaded ASO can silence MCT4 that overexpresses in tumor cells, resulting in efflux blockage of intracellular lactate and decrease of intracellular pH, which remarkably facilitates the cascade catalysis for amplified CDT. Meanwhile, such acidification triggers an MRI enhancement for reporting gene silencing. Results from in vivo testing further support the potential of our design for more effective CDT. This study offers different insights into the design and construction of advanced platforms for noninvasive imaging-guided treatment of a wide range of cancers.