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

Abstract

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.

Research Progress of Photothermal Nanomaterials in Multimodal Tumor Therapy

“…It has been widely used in photoacoustic imaging (PAI) and PTT for tumors (227)(228)(229). Wu et al (59) synthesized a glucose oxidase (GOx)-conjugated PANI nanoplatform (PANITG) for PTT for tumors. Under the irradiation of NIR laser, PANITG activates PTT in slightly acidic tumor microenvironments.…”

Nanozyme-laden intelligent macrophage EXPRESS amplifying cancer photothermal-starvation therapy by responsive stimulation

“…Tumor starvation therapy and photothermal therapy could promote and complement each other to achieve better combined treatment effect [ 31 , 33 ]. A series of nanoscale nanozymes, like hollow prussian blue nanoparticles loaded GOx nanosized biocatalyst [ 30 ], heptamethine cyanine dye (Cy7)-conjugated GOx nanoagents [ 33 ], GOx and tirapazamine co-loaded polydopamine doped poly(vinyl alcohol) microbubble [ 34 ], and GOx-conjugated polyaniline nanoplatform [ 35 ], have been reported to achieve combined tumor starvation and photothermal therapy. The GOx-mediated CST can block energy supply to tumor cells, which is beneficial to promote the PTT efficacy in mild temperature, whereas the enzymatic activity of GOx varies with temperature, and exhibits the optimal catalytic properties under PTT at local tumor.…”

A bimodal type of AgPd Plasmonic Blackbody Nanozyme with boosted catalytic efficacy and synergized photothermal therapy for efficacious tumor treatment in the second biological window

“…Photothermal effect is a phenomenon associated with material absorption of electromagnetic waves, resulting in the production of thermal energy (heat). This effect has been utilized for effective cancer treatment, i.e., photothermal therapy (PTT), by localized non-invasive therapeutic interventions through tumor-seated photothermal agents, which generate hyperthermia to kill tumor cells (via heating them to 42-45 °C or even higher) [40][41][42][43][44][45][46][47][48][49]. Indeed, marriage of PTT with nanozyme (using Fe 3 O 4 nanozyme and Pd nanosheet complexes, and platinum nanozymes coated with porous gold nanoshell) was observed to yield an enhanced tumor theranostics through visible or near infrared light in the first biological window (NIR-I, 650-950 nm) [50][51][52][53][54].…”