Near‐Infrared II Plasmonic Phototheranostics with Glutathione Depletion for Multimodal Imaging‐Guided Hypoxia‐Tolerant Chemodynamic‐Photocatalytic‐Photothermal Cancer Therapy Triggered by a Single Laser

Abstract

biomolecules and subsequently induce cancer cell death. [1,4,5] Hydroxyl radicals (•OH) is the most cytotoxic ROS in comparison with other counterparts such as superoxide anions (•O 2 − ), singlet oxygen ( 1 O 2 ), and peroxide (O 2 2−). [6] TME-triggered production of high-level •OH only at tumor sites instead of healthy tissues presents great advantages for anticancer treatments, including low invasiveness, minimal systemic toxicity, high hypoxia-tolerance, and most importantly high tumor specificity. Utilizing the features of abundant H 2 O 2 (typically ranging from 100 µm to 1 mm) and low catalase activity in the TME, in situ Fenton or Fenton-like reactions between transition metal ions (e.g., Fe 2+ , Mn 2+ , Cu + ) and intracellular H 2 O 2 produce •OH only at tumor sites, with negligible damage to healthy tissues. [7][8][9] Recent studies also showed that Fenton reactions with improved •OH generation efficiency could be achieved by either increasing the local tumor temperature or using light irradiation. [10,11] To further promote anticancer effects, "all-in-one" phototheranostic platforms combining diagnostic and therapeutic capabilities into a single entity have been developed by integrating ROS-based CDT with other therapeutic modalities (e.g., photodynamic therapy (PDT), chemotherapy, immunotherapy, photothermal therapy (PTT)), together with imaging modalities such as photoacoustic (PA) imaging, photothermal (PT) imaging, fluorescence imaging, magnetic resonance imaging, and computed topography (CT). [12][13][14][15][16][17][18] A successful marriage of these imaging and therapeutic modalities would yield bioimaging-guided on-demand cancer treatments with real-time tumor visualization, high controllability, low sideeffects, and excellent therapeutic efficacy.Despite those considerable advances, two critical issues still hinder clinical translation of ROS-mediated phototheranostic platforms that integrate photo-Fenton reaction involved CDT/ PDT, PTT, and optical imaging modalities. First, most of those previous "all-in-one" phototheranostic agents typically request multiple different laser wavelengths to implement imagingguided cancer treatments, which significantly increases the complexity and total cost of cancer treatments. [19,20] Second, Tumor microenvironment (TME)-activatable phototheranostics is highly desirable in cancer management but still remains challenging for clinical applications owing to the lack of multifunctional theranostic agents and the limited tissue penetration depth. Reported here is an "all-in-one" phototheranostic platform based on near-infrared II (NIR-II) dual-plasmonic Au@Cu 2−x Se core-shell nanocrystals (dpGCS NCs) for combined photoacoustic (PA)/photothermal (PT) imaging-guided chemodynamic therapy (CDT)/ photocatalytic therapy (PCT)/photothermal therapy (PTT) all triggered by a single NIR-II laser. The dpGCS NCs feature excellent NIR-II plasmonic and PT properties, which guarantee their capabilities of NIR-II PA and PT imaging for real-time visual observation of tumor si...

Biodegradable Amorphous Copper Iron Tellurite Promoting the Utilization of Fenton-Like Ions for Efficient Synergistic Cancer Theranostics

“…The intracellular •OH generation was also visually assessed using the 2′,7′-dichlorofluorescin diacetate (DCFH-DA) probe (Figure 2(E,ii)). 8 The 4T1 cells treated with saline show no noticeable green fluorescence, indicating negligible •OH in those cells. The 4T1 cells treated with a-CFT@IP6@BSA NPs possess a much high level of •OH than those treated with a-CFT@IP6 NPs, consistent with the results from the ESR and TA-based fluorescence measurements.…”

“…Electron spin resonance (ESR) spectroscopy was employed to examine •OH generation with 5,5-dimethyl-1-pyrroline N -oxide (DMPO) as the •OH capture probe, as shown in Figure A. , No obvious ESR signals were detected when a-CFT@IP6@BSA NPs are lacking. We can clearly see a quartet pattern with a peak intensity ratio of 1:2:2:1 in the ESR spectrum of the solution containing a-CFT@IP6@BSA NPs and H 2 O 2 , indicating the occurrence of Cu + -catalyzed Fenton-like reaction.…”

“…The chemodynamic agents play crucial roles in affecting the therapeutic efficacy of CDT. In recent decades, varieties of chemodynamic agents, such as iron-containing nanomaterials, − metal oxides, , copper chalcogenides, − metal–organic complexes, , have been developed with improved CDT therapeutic efficacy. Despite substantial advances, challenges hindering their clinical translation still exist, chiefly including limited therapeutic efficacy and biosafety issues.…”

Emerging Nanotheranostics for 5-Fluorouracil in Cancer Therapy: A Systematic Review on Efficacy, Safety, and Diagnostic Capability

“…Recently, a variety of on-demand near-infrared (NIR)-activated plasmonic NTA composed of metal nanomaterials (gold, platinum, palladium, copper, manganese, silver) had shown promising anticancer activity attributed to their photothermal and photodynamic properties. The metal nanoparticles efficiently convert light energy into highly localized heat energy (photothermal therapy) via a phenomenon known as localized surface plasmon resonance (LSPR) to destroy cancer cells and minimize collateral damage to adjacent normal tissues ( He et al, 2021a ; Cai et al, 2021 ; Shan et al, 2021 ; Shanmugam et al, 2021 ; Zhu et al, 2022 ). Plasmonic gold NTA-mediated photothermal therapy has also been tested in combination with chemotherapy and immunotherapy to achieve synergistic tumor inhibition in the 4T1 tumor model ( Zhang et al, 2020 ; Chen et al, 2021 ).…”

“…On the other hand, plasmonic NTA also possesses the ability to utilize light energy to generate reactive oxygen species (photodynamic therapy) for the destruction of tumors ( He et al, 2021b ; Chen et al, 2021 ; Shanmugam et al, 2021 ). In addition, plasmonic NTA enables real-time visualization of the tumor and precise tracking of NTA in the tumors via photoacoustic imaging to facilitate image-guided treatment ( He et al, 2021a ; Shan et al, 2021 ; Shanmugam et al, 2021 ; Zhu et al, 2022 ). These temporal and spatial information will provide guidance for physicians to optimize and tailor the treatment regimen for each patient to achieve personalized medicine.…”