NO-Driven Self-Propelled Nanomotors Augment Chemo-Immunotherapy and Transcatheter Arterial Embolization.

Abstract

Chemo-immunotherapy is often deemed a first-line treatment for clinical cancer patients. However, the major challenges of poor tumor penetration, multidrug resistance, and T-cell-related immune escape are still unresolved in clinical translation. Herein, we describe a nitric oxide (NO)-driven nanomotor that integrates bioinspired self-propulsion and immunosuppression alleviation for augmented chemo-immunotherapy. As demonstrated with two types of mouse tumor models, this nanomotor can be excited in response to the tumor microenvironment, which allows for enhanced drug penetration, sustained NO release, and immune cell infiltration within the tumor for tumor growth inhibition and synergistic immune checkpoint blockade. In addition, the nanomotor achieves interventional transcatheter arterial embolization therapy and boosted immunity in a VX2 orthotopic rabbit liver cancer model. The versatility and potency of the nanomotor validate its future applications in translational anticancer nanomedicine.