Phototherapy, including
photodynamic therapy (
PDT) and
photothermal therapy (PTT), has shown great promise for
cancer treatment in many preclinical studies. This study reports a nanoreactor designed for an enhanced mild temperature
phototherapy which utilizes multiple mechanisms including simultaneous
glucose consumption, oxygen supply,
glutathione (GSH) depletion and heat-resistance relief. The nanoreactor is prepared using an Fe-doped polydiaminopyridine (Fe-PDAP) nanozyme with an intrinsic
catalase-like activity coloaded with
glucose oxidase (GOx) and
indocyanine green (ICG). Evidence shows that
glucose plays a vital role in
tumor progression. Initiated by the breakdown of
glucose into
gluconic acid and H2O2 by GOx, Fe-PDAP promotes reoxygenation by catalyzing the reaction-supplied and
tumor cell-supplied H2O2 into O2, which then enhances the O2-dependent
PDT. Moreover, Fe-PDAP depletes GSH in
tumor cells for more efficient
reactive oxygen species (ROS) production. Meanwhile, the heat resistance of
tumor cells is relieved by GOx-induced
glucose exhaustion and
heat shock protein (HSP) reduction, improving the efficiency of PTT. In particular, the nanoreactor also serves as a
contrast agent for fluorescence, photoacoustic, and magnetic resonance multimodal imaging. Consequently, this nanoreactor efficiently inhibits
tumor growth through mild temperature
phototherapy under multimodal imaging guidance, resulting in successful
tumor ablation with minimal systemic toxicity.