Jahn-Teller distortion-engineered self-propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapy.

Mitochondrial metabolism plays a pivotal role in tumor progression, yet effective therapeutic targeting remains constrained by limited tissue penetration and lack of spatiotemporal control. Herein, we present Jahn-Teller distortion-engineered, self-propelled nanorobots (IDP@Z@AP) that integrate catalytic oxygen generation, mitochondria-targeted drug delivery, and real-time 3D NIR-II photoacoustic (PA) imaging for precision tumor therapy. The nanorobots are fabricated by co-encapsulating a NIR-II photothermal agent (IR1048) and a mitochondria-targeting chemotherapeutic (DOX-TPP) within a ZIF-8 framework, followed by in situ anchoring of ultrasmall AuPt bimetallic nanozymes. Pt-induced Jahn-Teller distortion modulates the electronic structure of AuPt, enhancing glucose oxidase- and catalase-like activities. Under NIR-II laser irradiation, photothermal-enhanced cascade catalysis drives autonomous motion and catalyzes intratumoral O(2) generation, facilitating deep tumor infiltration. In vitro studies reveal efficient mitochondrial targeting, resulting in significant mitochondrial membrane depolarization, intracellular ATP depletion, and suppressed cell migration and invasion. In vivo, 3D NIR-II PA imaging enables noninvasive visualization of nanorobot biodistribution and real-time mapping of catalytic oxygen generation within tumor tissues. This nanorobotic platform effectively modulates tumor hypoxia and enhances chemotherapeutic delivery to mitochondria, ultimately achieving potent tumor suppression. The work offers a smart, catalytically driven, mitochondria-targeted strategy with real-time therapeutic feedback for subcellular-level cancer therapy.