Enzyme-Engineered Conjugated Polymer Nanoplatform for Activatable Companion Diagnostics and Multistage Augmented Synergistic Therapy

Companion diagnostics (CDx) provides critical information for precision medicine. However, current CDx is mostly limited to in vitro tests, which cannot accurately evaluate the disease progression and treatment response in real time. To overcome this challenge, herein a glucose oxidase (GOx)-engineered conjugated polymer (polyaniline, PANI) nanoplatform (denoted as PANITG) is reported for activatable imaging-based CDx and multistage augmented photothermal/starvation synergistic therapy. PANITG comprises a pH-activatable conjugated polymer as a photothermal convertor and photoacoustic (PA) emitter, a GOx as a cancer starvation inducer as well as a H2O2 and acid producer, and a H2O2-cleavable linker as a switch for GOx activity. The in vivo PA imaging and photothermal therapy abilities are activated by acidic tumor microenvironment and self-augmented by the reaction between GOx and glucose. Meanwhile, the photothermal effect will enhance the GOx activity in turn. Such multistage augmentation of the therapeutic effects will facilitate effective cancer management. In addition, the in vivo PA imaging with PANITG reveals the tumor pH level which is correlated to the efficiency of the photothermal therapy and to the catalytic activity of GOx at each stage, enabling real-time activatable CDx.

Automated summary

This study presents a glucose oxidase-engineered nanoplatform for activatable imaging-based companion diagnostics and multistage augmented photothermal/starvation synergistic therapy. The nanoplatform utilizes a pH-activatable conjugated polymer as a photothermal converter and photoacoustic emitter, glucose oxidase as a cancer starvation inducer, and a H2O2-cleavable linker as a switch for enzyme activity. The in vivo imaging and therapy abilities are activated by the acidic tumor microenvironment and self-augmented by the reaction between glucose oxidase and glucose.