Enzyme-Powered Janus Upconversion Nanomotors for Deep Tumor Penetration and Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is an emerging cancer treatment that utilizes photosensitizers to generate reactive oxygen species (ROS) within tumor tissues upon activation. However, photoexcitation of conventional PDT is toughly restricted by the barrier of tissue penetration. Upconversion nanoparticles (UCNPs) present a promising solution by converting near-infrared (NIR) light into visible emissions, enabling deeper tissue penetration. Despite this advancement, the passive delivery of photosensitizer nanocarriers remains inefficient in overcoming the barriers posed by the tumor microenvironment. In this study, we present urease-driven Janus UCNPs nanomotors that integrate self-propulsion with NIR-activated PDT. These nanomotors are fabricated by asymmetrically growing a mesoporous silica (mSiO2) shell on UCNPs, which emit strong red light at 660 nm when excited by 980 nm NIR light. This emission activates the visible-light-absorbing photosensitizer chlorin e6 (Ce6) within the mSiO2 shell. Functionalization with urease enables the Janus urease-UCNPs@mSiO2-Ce6 (UUmSC) nanomotors to propel themselves by catalyzing the decomposition of urea into carbon dioxide and ammonia, driving motion via a self-diffusiophoretic mechanism. This active propulsion enhances cellular uptake and facilitates deep tissue penetration, improving targeted delivery of the photosensitizer. Upon irradiation with 980 nm NIR light, the visible light emitted by UCNPs activates Ce6, triggering ROS production for tumor treatment. Notably, enzyme-powered nanomotors significantly enhance PDT efficacy, offering a precise and minimally invasive strategy for efficient cancer therapy.

Note:
Funding declaration: This work was financially supported by the National Natural Science Foundation of China (No. 22462021). Start-Up Grant of Wenzhou Institute, University of Chinese Academy of Sciences.

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Keywords: Janus nanomotor, Upconversion, Targeted delivery, Tumor penetration, Photodynamic therapy