Near-Infrared Light-Accelerated Bioorthogonal Drug Uncaging and Photothermal Ablation by Anisotropic Pd@Au Plasmonic Nanorods
M. Carmen Ortega‐Liebana, Jana Trávníčková, Catherine Adam, Davir González-Calderón, Álvaro Lorente‐Macías, Charles Lochenie, Raúl Arenal, E. Elizabeth Patton, Asier Unciti‐Broceta
Abstract
High Resolution Image Download MS PowerPoint Slide Selective activation of chemotherapeutics at the tumor site via bioorthogonal catalysis is a promising strategy to reduce collateral damage to healthy tissues and organs. Despite significant advances in this field, targeted drug activation by transition-metal catalysts is still limited by insufficient spatiotemporal control over the metal-mediated uncaging process. Herein, we report the development of anisotropic Pd@Au plasmonic nanorods with the capacity to accelerate dealkylation reactions under near-infrared (NIR) irradiation, thereby enabling precise control over when and where these catalytic devices are switched on. We also show that the stability and in cellulo chemical properties of Pd@Au nanorods are enhanced by Au–S functionalization with PEGylated phospholipids and report the development of a novel masking group for prodyes and prodrugs: the POxOC group, designed to improve physicochemical properties and the rate of the Pd-triggered dye/drug release process. NIR-photoactivation of lipo-Pd@Au nanorods is able to catalyze the uncaging of inactive drug precursors and release heat to the environment, killing cancer cells in culture and xenografted in zebrafish. This work provides a novel targeted strategy for photothermal chemotherapy by NIR-laser focalization.