A Tumor‐Microenvironment‐Activated Nanozyme‐Mediated Theranostic Nanoreactor for Imaging‐Guided Combined Tumor Therapy

Abstract

Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme‐mediated 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) loaded ABTS@MIL‐100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging‐guided combined tumor therapy. The as‐constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme‐mediated “two‐step rocket‐launching‐like” process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H2O2 level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor‐triggered PTT. More importantly, the H2O2‐activated and acid‐enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme‐involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.

Tumor‐Microenvironment‐Triggered Ion Exchange of a Metal–Organic Framework Hybrid for Multimodal Imaging and Synergistic Therapy of Tumors

“…[ 8–18 ] However, most of reported NTAs suffer from their poor tumor specificity and unsatisfactory therapeutic efficiency due to the severe background interference during metabolism caused by the “always on” model. [ 19–21 ] To solve this problem, in situ NTA synthesis strategy to activate pro‐NTAs (precursor of NTAs) into NTAs at desired locations has attracted increasing attention. [ 20,22–25 ] Based on specific chemical reactions, NTAs could be synthesized only in tumor tissues to minimize the background interference.…”

“…[ 19–21 ] To solve this problem, in situ NTA synthesis strategy to activate pro‐NTAs (precursor of NTAs) into NTAs at desired locations has attracted increasing attention. [ 20,22–25 ] Based on specific chemical reactions, NTAs could be synthesized only in tumor tissues to minimize the background interference.…”

“…have been used to carry small‐molecule theranostic agents. [ 20,31–34 ] Moreover, porphyrin‐based MOFs have been widely used as NTAs for fluorescence imaging and PDT in tumor therapy. [ 28,35–38 ] Compared to small‐molecule theranostic agents, NTAs composed of MOF nanomaterials demonstrate stronger tumor retention with an enhanced permeability and retention (EPR) effect.…”

Nanozymes: A New Disease Imaging Strategy

“…Nanozyme probes have also been broadly developed for disease therapeutic monitoring. For example, in 2019, Chen's group prepared a tumor-microenvironment-activated nanozyme-mediated theranostic nanoreactor for imaging-guided combined tumor therapy (Liu F. et al, 2019). In their work, the constructed activatable nanoreactors achieved non-invasive imaging of tumor progression by using nanozyme-mediated photoacoustic imaging signal and photothermal therapy (PTT) function and the AMP NPs were at a dose of 10 mg/kg, 200 µL (Figure 3B).…”

“…(B) Representative nanozyme-based tumor photoacoustic imaging images. Reproduced with permission from ref(Liu F. et al, 2019), © 2019, John Wiley and Sons. (C) Carbon-gold hybrid nanozymes for real-time imaging, photothermal/photodynamic and nanozyme oxidative therapy of tumors.…”