Highly Efficient GSH-Responsive “Off–On” NIR-II Fluorescent Fenton Nanocatalyst for Multimodal Imaging-Guided Photothermal/Chemodynamic Synergistic Cancer Therapy

Abstract

Accurate diagnosis and effective treatment of malignant tumors under the interference of complex and diverse tumor microenvironments (TMEs) have become the focus of research. Herein, an innovative TME-activated biomimetic nanocatalyst with quad-modal imaging capabilities of second near-infrared (NIR-II) “turn-on” fluorescence imaging, magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and photothermal imaging (PTI) was designed and developed for self-enhanced photothermal/chemodynamic synergistic therapy. The catalyst was fabricated by loading glucose oxidase (GOD) and Ag2S quantum dots (QDs) on MnO2 nanosheets and coating them with a 4T1 cell membrane (AMG@CM), which enables them to successfully escape immune clearance and have appealing tumor-targeting ability and biocompatibility. The NIR-II fluorescence at 1130 nm of Ag2S QDs quenched by MnO2 could be recovered in vivo through the glutathione (GSH)-induced degradation of MnO2, enabling excellent TME-responsive tumor visualization. Simultaneously, the released Mn2+ can catalyze H2O2 to produce abundant hydroxyl radicals (•OH), achieving photothermal synergistically enhanced chemodynamic therapy (CDT) under NIR-II radiation. Moreover, the CDT could be self-enhanced by GOD due to the extra produced H2O2. This work demonstrates a novel and highly efficient multimodal imaging-guided integrated treatment strategy for dual-enhanced CDT tumor precise diagnosis and treatment.

Nanosystems for chemodynamic based combination therapy: Strategies and recent advances

“…With the rapid expansion of chemistry and materials science, nanotechnology shows great potential to overcome the limitations of conventional tumor therapy, and nanosystems (or nanotherapeutics) are regarded as one of the most promising strategies for better tumor treatment (Zhang P. et al, 2022). The recent reports have revealed that the combination therapy strategies with CDT nanosystems can optimize the therapy effects and minimize the toxicity and adverse effects of treatment (He et al, 2021;Yang et al, 2021;Liu Y. et al, 2022;Hao et al, 2022).…”

“…In addition, the imbalance of calcium transport channels caused by oxidative stress further promoted the calcification, inducing the necrosis of tumor cells (also named as ion interference therapy). Therefore, during ROS generation process, the Fenton-like reaction generated by Cu 2+ is synergistic with the mitochondrial dysfunction induced by Ca 2+ (Liu B. et al, 2022).…”

“…In addition to the photothermal treatment effect, glucose oxidase (GOD) can oxidize excess glucose to H 2 O 2 , and at the same time, the released Mn 2+ can catalyze H 2 O 2 to generate abundant •OH through Fenton-like reaction. Therefore, photothermal enhanced chemodynamic therapy can be achieved under near-infrared light irradiation ( Li et al, 2022 ).…”

Dual-Targeting and Multimodal Imaging-Guided Photothermal/Chemodynamic Synergistic Therapy Boosted by Ascorbic Acid-Induced H2O2 in Situ Self-Supply

“…To achieve precise tumor visualization and localization, constructing multimodal imaging to exploit the advantages of various imaging techniques is considered an effective strategy. Recently, our group has reported a kind of water-soluble Ag 2 S quantum dots (QDs) with highly bright NIR-II fluorescence , and developed a multimodal imaging bioprobe with NIR-II “turn-on” fluorescence imaging, photothermal imaging (PTI), photoacoustic imaging (PAI), and MRI capabilities …”

Chemical Cyclic Amplification: Hydroxylamine Boosts the Fenton Reaction for Versatile and Scalable Biosensing

“…At the same time, ROS are generated in organisms as metabolites or signaling molecules during cellular metabolism or in response to environmental stimuli . Furthermore, due to the unique oxidative properties of • OH, it has a wide range of applications in the degradation of environmental pollutants, cancer therapy, and analytical chemistry . Therefore, sensitive and accurate detection of • OH is also an important task in biosensing.…”