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

TLDR

Activatable theranostic agents triggered by the tumor microenvironment offer higher specificity and sensitivity. The study develops activatable nanozyme‑mediated ABTS‑loaded AMP nanoreactors for imaging‑guided combined tumor therapy. AMP NRs are activated by the tumor microenvironment via a nanozyme‑mediated two‑step rocket‑launching‑like process that turns on photoacoustic imaging and photothermal therapy, while simultaneously generating hydroxyl radicals and depleting glutathione to enable enhanced chemodynamic therapy. The AMP NRs exhibit tumor specificity by responding to H₂O₂ and acidity, sparing normal tissues, and their combined imaging, photothermal, and chemodynamic functions suggest a promising platform for intelligent, accurate, and noninvasive cancer theranostics.

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 H2 O2 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 H2 O2 -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.