Oxygen and Heat Dual‐Driven Stomatocyte Nanomotors for Highly Efficient Inflammation‐Relieved Breast Tumor Photothermal Therapy

Abstract The development of nanomedicines for autonomous motion‐promoted deep tumor treatment without the generation of inflammatory damage to normal tissues remains an extreme challenge. Herein, the design of an oxygen/heat dual‐driven stomatocyte nanomotor is showcased by integrating gold (Au) nanoparticles (NPs) and cerium oxide (CeO_2‐x) NPs into artificial stomatocytes (Ce/Au‐Stomatocytes) that are further coated with cancer cell membranes (CM). The prepared Ce/Au‐Stomatocytes with anisotropic morphology possess multiple enzyme‐mimetic activities and desired oxygen/heat dual‐driven motion performances upon laser irradiation, and can actively accumulate at the tumor site through CM‐mediated homotypic targeting. Importantly, the CeO_2‐x NPs inside stomatocytes enable oxygen production in the tumor microenvironment, thus relieving hypoxia and helping the stomatocytes deeply enter the tumor region via oxygen‐induced motion. Upon laser irradiation of the tumor region, the surface‐coated Au NPs can be activated to generate heat to induce thermophoretic motion for highly efficient photothermal therapy (PTT) via motion‐enhanced tumor penetration. More importantly, the CeO_2‐x NPs can alleviate the abnormal inflammatory responses triggered by PTT, thereby reducing skin damage after laser irradiation. Overall, this study provides a new approach to developing bionic, functional, and oxygen/heat dual‐driven nanomotors with promising performance for enhanced antitumor PTT without the generation of a non‐desired inflammation effect.