Spatiotemporal Ultrasound-Driven Bioorthogonal Catalytic Therapy.
Lili XiaMeng ChenCaihong DongFeipeng LiuHui HuangWei FengYu ChenPublished in: Advanced materials (Deerfield Beach, Fla.) (2022)
Bioorthogonal chemistry, referring to the rapid and selective synthesis of imaging and/or therapeutic molecules in live animals via transition metal-mediated non-natural chemical transformation without disrupting endogenous reactions, has greatly expanded the tools and techniques for biomedicine. However, owing to safety concerns associated with metal toxicity, selectivity, sensitivity and stability, efficient bioorthogonal reactions that can be reliably executed in complex biological environments remain challenging. In this study, an intelligent, versatile bioorthogonal catalyst based on ultrasmall poly(acrylic acid)-modified copper nanocomplexes (Cu@PAA NCs) to achieve high spatiotemporal catalytic efficacy is established. The catalytic activity of the Cu@PAA NCs can be reversibly regulated via valence state interconversion between Cu(II) and Cu(I) under exogenous ultrasound irradiation, promoting off-target prodrug activation in lesion sites through the Cu(I)-catalyzed azide-alkyne cycloaddition reaction. Moreover, ultrasound-triggered electron-hole separation endows the Cu@PAA NCs with robust sonosensitizing ability for sonodynamic therapy. Furthermore, the Cu@PAA NCs exhibit enhanced contrast in magnetic resonance and photoacoustic imaging. Notably, the renal-clearable Cu@PAA NCs exhibit intrinsically benign biocompatibility. This spatiotemporally ultrasound-mediated bioorthogonal catalysis not only expands the repertoire of in situ therapeutic agents but also provides a new avenue for disease theranostics.
Keyphrases
- magnetic resonance
- metal organic framework
- aqueous solution
- magnetic resonance imaging
- high resolution
- stem cells
- room temperature
- oxidative stress
- contrast enhanced
- radiation therapy
- photodynamic therapy
- gold nanoparticles
- fluorescence imaging
- cell therapy
- electron transfer
- structural basis
- loop mediated isothermal amplification