Lactate-driving Pt nanoflower with positive chemotaxis for deep intratumoral penetration

The deep penetration in response to specific intratumoral conditions holds considerable potential in achieving a more effective therapy. Lactate is mainly produced by exuberant-metabolism tumor cells growing in the deep center of solid tumor, which would form the characteristic of higher-level lactate deep inside tumor in distance with blood vessels. Herein, inspired by the in vitro directional chemotaxis of enzyme-powered nanomotor driven by substrate gradient, a novel lactate oxidase (LOX)-powered Pt Nanoflowers (Pt NFs) was developed to achieve deep intratumoral penetration triggered by the lactate-driving positive chemotaxis that was confirmed both in vitro and in vivo for the first time. Besides, LOX-powered Pt NFs with self-oxygenation could achieve a more thorough effect on hypoxic relief via the cascading catalysis: (1) the orthotopic extra H2O2 production from lactate catalyzed by LOX, and (2) the effective conversion of both extra-supplement and endogenous H2O2 into O2 catalyzed by Pt NFs, further overcoming the hypoxia-induced radioresistance. Meanwhile, the X-ray radiation deposited inside Pt NFs could improve low-dose radiotherapy effect with increasing ROS level and enhancing nuclear DNA damage. Collectively, this work would provide a blueprint for developing substrate gradient-driving "smart" delivery systems and radiosensitization strategy.