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 Fe3O4 nanocapsules (Fe3O4@DMSN), further modified with poly(vinylpyrrolidone) (PVP) to improve the solubility and biocompatibility, defined as ACP-Fe@D 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 H2O2 in the tumor microenvironment and the self-depletion intracellular GSH endow ACP-Fe@D 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 H2O2-activated and tumor microenvironment improved profiles endow the nanocapsules to be specific to tumors, avoiding the damage to normal tissue. These prominent characteristics of ACP-Fe@D NCs may open up a new trail to explore activatable nanoplatform for imagingdirected smart, precise, and noninvasive tumor theranostics.