Engineering Metal–Organic Framework Hybrid AIEgens with Tumor-Activated Accumulation and Emission for the Image-Guided GSH Depletion ROS Therapy

Abstract

Aggregation-induced emission (AIE)-active luminogens (AIEgens) have demonstrated exciting potential for the application in cancer phototheranostics. However, simultaneously achieving tumor-activated bright emission, enhanced reactive oxygen species (ROS) generation, high tumor accumulation, and minimized ROS depletion remains challenging. Here, a metal−organic framework (MOF) hybrid AIEgen theranostic platform is designed, termed A-NUiO@DCDA@ZIF-Cu, composed of an AIEgen-loaded hydrophobic UiO-66 (A-NUiO@DCDA) core and a Cu-doped hydrophilic ZIF-8 (ZIF-Cu) shell. The fluorescence emission and therapeutic ROS activity of AIEgens are restrained during delivery. After uptake by tumor tissues, ZIF-Cu decomposition occurs in response to an acidic tumor microenvironment (TME), and the hydrophobic A-NUiO@ DCDA cores self-assemble into large particles, extremely increasing the tumor accumulation of AIEgens. This results in enhanced fluorescence imaging (FLI) and highly improved 1 O 2 generation ability during photodynamic therapy (PDT). Meanwhile, the released Cu 2+ reacts to glutathione (GSH) to generate Cu + , which provides an extra chemodynamic therapy (CDT) function through Fenton-like reactions with overexpressed H 2 O 2 , resulting in the GSH depletion-enhanced ROS therapy. As a result of these characteristics, the MOF hybrid AIEgens can selectively kill tumors with excellent efficacy.

Nanoscale metallic‐organic frameworks as an advanced tool for medical applications: Challenges and recent progress

“…[ 128 ] A suitable method for early detection and treatment of cancer is phototheranostics, which is based on deep tissue imaging in combination with PTT and PDT. [ 129 ] In this regard, Dong et al [ 130 ] developed emission driven aggregation active luminogens (AIEgens) for cancer phototheranostic application. In particular, a core consisting of AIEgen‐loaded UiO‐66 and a shell including ZIF‐Cu were synthesized.…”

Inorganic‐Based Aggregation‐Induced Luminescent Materials: Recent Advances and Perspectives

“…Dong et al designed a program‐responsive diagnostic platform based on core–shell AIE@MOFs for synergistic treatment of cancer (Figure 7C). [ 164 ] Using AIEgens and terephthalic acid as linkers and Zr 4+ as metal nodes, fluorescent A‐NUiO was synthesized and hydrophobized with hydrophobic dodecanedioic acid (DCDA). Afterward, Cu‐doped ZIF‐8 was further encapsulated, and the weaker emitting A‐NUiO@DCDA@ZIF‐Cu was collected.…”

“…C) Synthetic and TME-triggered scheme of A-NUiO@DCDA@ZIF-Cu for PDT and CDT. Reproduced with permission [164]. Copyright 2022, American Chemical Society.…”

Glutathione depletion-mediatedin situtransformation of Prussian blue nanocubes for enhanced tumor-specific imaging and photoimmunotherapy

“…[14][15][16] Despite the precise treatment obtained, the glutathione (GSH)-enriched TME compromised the ROS and minimized the PDT outcome. [17][18][19][20][21] Therefore, it is vital to integrate the in situ transformation of phototheranostic agents with GSH depletion into one platform for augmenting tumor-specific imaging and phototherapy efficacy.…”