Black Titania Janus Mesoporous Nanomotor for Enhanced Tumor Penetration and Near-Infrared Light-Triggered Photodynamic Therapy.

Abstract

Thanks to their excellent photoelectric characteristics to generate cytotoxic reactive oxygen species (ROS) under the light-activation process, TiO₂ nanomaterials have shown significant potential in photodynamic therapy (PDT) for solid tumors. Nevertheless, the limited penetration depth of TiO₂-based photosensitizers and excitation sources (UV/visible light) for PDT remains a formidable challenge when confronted with complex tumor microenvironments (TMEs). Here, we present a H₂O₂-driven black TiO₂ mesoporous nanomotor with near-infrared (NIR) light absorption capability and autonomous navigation ability, which effectively enhances solid tumor penetration in NIR light-triggered PDT. The nanomotor was rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of a NIR light-responsive black TiO₂ nanosphere and an enzyme-modified periodic mesoporous organosilica (PMO) nanorod that wraps around the TiO₂ nanosphere. The overexpressed H₂O₂ can drive the nanomotor in the TME under catalysis of catalase in the PMO domain. By precisely controlling the ratio of TiO₂ and PMO compartments in the Janus nanostructure, TiO₂&PMO nanomotors can achieve optimal self-propulsive directionality and velocity, enhancing cellular uptake and facilitating deep tumor penetration. Additionally, by the decomposition of endogenous H₂O₂ within solid tumors, these nanomotors can continuously supply oxygen to enable highly efficient ROS production under the NIR photocatalysis of black TiO₂, leading to intensified PDT effects and effective tumor inhibition.