Tumor microenvironment activated glutathione self-depletion theranostic nanocapsules for imaging-directed synergistic cancer therapy

Activatable nanosystem for cancer therapy are of considerable attention in the field of theranostics. Nevertheless, constructing activatable nanosystem with specific response performance and turn “on–off” treatment mode still remains an enormous challenge. Here, we developed a cascade reaction nanomedicine for highly efficient cancer theranostics by constructing and delivering multifunctional activatable nanocapsules into the tumor region. 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS, activatable agent) and camptothecin (CPT, chemotherapeutic drug) have been encapsulated into large pore-sized dendritic macroporous silica coated Fe 3 O 4 nanocapsules (Fe 3 O 4 @DMSN), further modified with poly(vinylpyrrolidone) (PVP) to improve the solubility and biocompatibility, defined as [email protected] NCs. The prepared nanocapsules can be specifically responded to tumor microenvironment by a nanozyme-catalyzed two-step acceleration process to turn on its hyperthermia effect and imaging performance due to the production of oxidized ABTS, simultaneously. Moreover, the generating hydroxyl radicals are attributed to the overexpressed H 2 O 2 in the tumor microenvironment and the self-depletion intracellular GSH endow [email protected] with the capability of promoted chemodynamic therapy, therefore resulting in significant therapeutic effect in connection with chemotherapy and tumor microenvironment-mediated photothermal therapy. What’s more, the H 2 O 2 -activated and tumor microenvironment improved profiles endow the nanocapsules to be specific to tumors, avoiding the damage to normal tissue. These prominent characteristics of [email protected] NCs may open up a new trail to explore activatable nanoplatform for imaging-directed smart, precise, and noninvasive tumor theranostics.