Yolk‐Shell Structured Nanoflowers Induced Intracellular Oxidative/Thermal Stress Damage for Cancer Treatment

Abstract Cancer cells, with unique their metabolism, frequently exhibit a high level of redox homeostasis, which could be a feasible target for cancer treatment. Here, liquid metal (LM) nanoparticles are used as a template to guide the growth of yolk‐shell structured LM@MnO₂ (LMN). With yolk‐shell structures, LMNs is applied to load with cinnamaldehyde (CA) (CLMN) and further coated with hyaluronic acid (HA) to construct the CA&LM@MnO₂‐HA nanoflowers (CLMNF) for cancer targeted treatment. Owing to the urchin‐like structured shell, it is found that the obtained CLMNF particles rapidly deplete glutathione (GSH) and produce manganese ions, which further facilitate hydrogen peroxide converting into hydroxyl radical (·OH) for cancer cell killing. Accompanying the depletion of GSH, the balance of intracellular redox homeostasis tilts towards oxidation, resulting in amplified oxidative damage caused by CA, eventually, leading to the apoptosis of cancer cells. Combined with the remarkable near infrared (NIR) photothermal conversion properties, the novel structured CLMNF exhibits favorable inhibition of tumors in vivo, indicating that using nanoflowers to induce intracellular oxidative/thermal stress damage could be a promising strategy for anticancer treatment.