Engine-cargo structured nanotrucks for advanced phototherapy by alleviating hypoxia and penetration barriers via...

Photodynamic therapy (PDT) holds significant promise for tumor treatment, yet its efficiency is still limited by shallow light penetration and tumor hypoxia. Herein, this study develops a Janus-typed nanotruck with an "engine-cargo" structure, where an upconversion nanoparticle is asymmetrically coated by a mesoporous silica shell using a special surfactant-templating method. Upon further loading with catalase (CAT) and photosensitizer (MC540), the obtained nanotruck enables to convert tumor-overexpressed H₂O₂ into oxygen gas, which not only propels the nanoparticle to enhance cellular uptake and tissue penetration but also alleviates tumor hypoxia. Thanks to the synergistic effect of particle motion and oxygen production, both in vitro and in vivo results showed that the ROS (reactive oxygen species) generation was significantly amplified under 980 NIR light illumination, which greatly enhanced PDT efficiency in tumor treatment. It is believed that this study demonstrates a promising strategy to alleviate limitations of traditional PDT and provides a more effective and targeted approach to tumor therapy.