Programmable starving-photodynamic synergistic cancer therapy

Abstract

Synergistic therapy combines multiple therapeutic approaches in one shot, thus could significantly amplify the therapeutic effects. However, how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management. Herein, a nanoagent composed of glucose oxidase (GOx) and upconversion nanoparticles (UCNPs) were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis. In this nanoagent, GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H 2 O 2. The glucose depletion induced "starvation" in cancer cells and caused cell death. Afterwards, the generated H 2 O 2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm. The toxic hydroxyl radicals produced by photolysis further induced cancer cell death. Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy. This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.

Enzyme Mimics for Engineered Biomimetic Cascade Nanoreactors: Mechanism, Applications, and Prospects

“…[95] To realize "1 + 1 > 2" tumor therapy efficiency, nanoreactors based on GOx-CAT cascade catalysis have been constructed for enhanced starvation-PDT synergistic cancer therapy. [170] For example, Liu et al prepared two nanozymeengineered porphyrin MOFs with both GOx-and CAT-like activity, which were used for catalytic cascade-enhanced starvation-PDT synergistic therapy (Figure 15). CAT-mimicking PtNPs were sandwiched by PCN and then GOx-like AuNPs were embedded into the outer shell, which was further modified with folic acid (FA) to obtain a cascade nanoreactor (P@Pt@P-Au-FA).…”

“…[ 95 ] To realize “1 + 1 > 2” tumor therapy efficiency, nanoreactors based on GOx‐CAT cascade catalysis have been constructed for enhanced starvation‐PDT synergistic cancer therapy. [ 170 ] For example, Liu et al. prepared two nanozyme‐engineered porphyrin MOFs with both GOx‐ and CAT‐like activity, which were used for catalytic cascade‐enhanced starvation‐PDT synergistic therapy ( Figure ).…”

Glucose Oxidase‐Related Cancer Therapies

“…Under 980 nm laser irradiation, UCNPs can convert low‐energy photons to high‐energy invisible ultraviolet photons, which will trigger the photolysis of H 2 O 2 . [ 64 ]…”

Recent Advances in Biomaterial Scaffolds for Integrative Tumor Therapy and Bone Regeneration

“…[125] To enhance tumor therapeutic efficacy and decrease side effects, synergistic therapy which combines appropriate two or more modalities have been proposed to combat tumors. [126][127][128] To date, much effort has been devoted to developing smart nanoplatforms for synergistic tumor therapy, and more advances have been ; the corresponding confocal images of live and dead tumor cells which were treated with multi-hyperthermia treatments (c). C) Confocal images (upper) and SEM images (lower) of rBMSCs which were incubated with different groups of scaffolds.…”

“…[ 125 ] To enhance tumor therapeutic efficacy and decrease side effects, synergistic therapy which combines appropriate two or more modalities have been proposed to combat tumors. [ 126–128 ] To date, much effort has been devoted to developing smart nanoplatforms for synergistic tumor therapy, and more advances have been achieved. For example, Miao et al.…”