Catalysis at the skin interface: Dissolving single-atom nanozyme microneedles for superficial skin malignancies therapy

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. The management of cSCC high-risk variant, aggressive and metastatic, is particularly challenging due to the limitations of current therapies, including recurrence after surgery, functional damage, and poor efficacy of systemic treatments in advanced stages. In response to these limitations, this study constructed a multifunctional synergistic therapeutic microneedle system (defined as Ce/Au SMNs) based on a Ce single-atom material decorated with Au nanoparticles (Ce SAs/Au NPs). Engineered soluble microneedles cause minimal trauma, and enable slow drug release in the tumor, ensuring low side effects and accurate local administration. Stimulus-responsive nanoparticles exhibited enzyme-like activities in response to the tumor microenvironment, including glucose oxidase (GOD)-, peroxidase (POD)-, catalase (CAT)-, oxidase (OD)- and glutathione peroxidase (GSH-Px)-like activities. Microneedle insertion drives a self-amplifying catalytic cycle. This cycle not only accelerates intracellular glucose consumption but also disrupts the cellular antioxidant defense mechanism. Additionally, Ce SAs/Au NPs have a photothermal conversion efficiency of up to 42.5%. This photothermal effect further enhances their enzyme-like activities, ultimately leading to apoptosis and inhibiting tumor growth. This work proposed a novel and promising approach for developing an efficient and low-toxicity treatment method to address superficial skin malignancies.