Chemotherapy-enabled/augmented cascade catalytic tumor-oxidative nanotherapy

Tailored to the specific tumour microenvironment, which involves acidity and the overproduction of hydrogen peroxide, advanced nanotechnology has been introduced to generate the hydroxyl radical (. OH) primarily for tumour chemodynamic therapy (CDT) through the Fenton and Fenton-like reactions. Numerous studies have investigated the enhancement of CDT efficiency, primarily the increase in the amount of . OH generated. Notably, various strategies based on the Fenton reaction have been employed to enhance . OH generation, including nanomaterials selection, modulation of the reaction environment, and external energy fields stimulation, which are discussed systematically in this Minireview. Furthermore, the potential challenges and the methods used to facilitate CDT effectiveness are also presented to support this cutting-edge research area.

The reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, a photosensitizer (PS) and oxygen, which greatly favors the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) the limited penetration depth of light, which restricts traditional PDT to superficial tumours; (ii) oxygen reliance does not allow PDT treatment of hypoxic tumours; (iii) light can complicate the phototherapeutic outcomes because of the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects from undesirable white-light activation and self-catalysation of traditional PSs. Recent advances in nanotechnology and nanomedicine have provided new opportunities to develop ROS-generating systems through photodynamic or non-photodynamic procedures while tackling the challenges of the current PDT approaches. In this review, we summarize the current status and discuss the possible opportunities for ROS generation for cancer therapy. We hope this review will spur pre-clinical research and clinical practice for ROS-mediated tumour treatments.