NIR-II responsive PEGylated nickel nanoclusters for photothermal enhanced chemodynamic synergistic oncotherapy.

Rationale: All kinds of non-metal and metal-based nanozymes have been extensively explored as Fenton agents for Chemodynamic therapy (CDT). However, the low catalytic efficiency of non-metallic nanozymes and the susceptibility to oxidation and long-term toxicity of metallo-nanozymes limit their potential in CDT. Methods: In this study, we report a magneto-solvothermal method to tune the crystallinity and shape of polyethylene glycol (PEG)-ylated urchin-like nickel nanoclusters (named as 9T-PUNNC) at a high magnetic field with an intensity of 9 T for enhanced combined photothermal-chemodynamic therapy. Results: The needle-like protrusions on the surface of 9T-PUNNC can effectively increase the reception of NIR light in second NIR window (NIR-II) and transform it into local hyperthermia, achieving effective photothermal treatment. The light and heat generated by NIR-II further promotes the release of Ni2+ and improves the ability of Ni2+-mediated chemodynamic therapy (CDT). In addition, the surface coating of PEG on the surface of 9T-PUNNC improves its stability and biocompatibility of nanocrystals. In vitro and in vivo results indicate that the 9T-PUNNC could efficiently kill tumor cells (nearly 12 times more than control group) and inhibit tumor growth (nearly 9 times smaller than control group) under NIR-II irradiation through the synergistic effect of combined treatments. Conclusions: we developed a novel synthetic strategy to tune crystallinity and shape of PUNNC for enhanced NIR-II responsive photothermal conversion efficiency and accelerated acid-induced dissolution for improved ·OH generation. Such 9T-PUNNC enable a combined chemodynamic-photothermal treatment to provide superior therapeutic efficacy due to their highly synergistic effect.

Exogenously Triggered Nanozyme for Real-Time Magnetic Resonance Imaging-Guided Synergistic Cascade Tumor Therapy.

The uncontrolled treatment process and high concentration of intracellular glutathione compromise the therapeutic efficacies of chemodynamic therapy (CDT). Here, iron oxide nanocrystals embedded in N-doped carbon nanosheets (IONCNs) are designed as a near-infrared light-triggered nanozyme for synergistic cascade tumor therapy. The IONCNs can absorb and convert 980 nm light to local heat, which induces the dissolution of iron oxide for generating Fe2+/Fe3+ in a weak acid environment, apart from thermal ablation of cancer cells. The formed Fe2+ takes on the active site for the Fenton reaction. The formed Fe3+ acts as glutathione peroxidase to magnify oxidative stress, improving the antitumor performance. The IONCNs can be used to visually track the treatment process via magnetic resonance imaging. Such IONCNs demonstrate great potential as an exogenously triggered nanozyme via an integrated cascade reaction for imaging-guided synergistic cancer therapy.

NIR-II Responsive Hollow Magnetite Nanoclusters for Targeted Magnetic Resonance Imaging-Guided Photothermal/Chemo-Therapy and Chemodynamic Therapy.

Phototherapy in the second near-IR (1000-1700 nm, NIR-II) window has achieved much progress because of its high efficiency and relatively minor side effects. In this paper, a new NIR-II responsive hollow magnetite nanocluster (HMNC) for targeted and imaging-guided cancer therapy is reported. The HMNC not only provides a hollow cavity for drug loading but also serves as a contrast agent for tumor-targeted magnetic resonance imaging. The acid-induced dissolution of the HMNCs can trigger a pH-responsive drug release for chemotherapy and catalyze the hydroxyl radical (·OH) formation from the decomposition of hydrogen peroxide for chemodynamic therapy. Moreover, the HMNCs can adsorb and convert NIR-II light into local heat (photothermal conversion efficacy: 36.3%), which can accelerate drug release and enhance the synergistic effect of chemo-photothermal therapy. The HMNCs show great potential as a versatile nanoplatform for targeted imaging-guided trimodal cancer therapy.

Graphitic Carbon Nitride Quantum Dots Embedded in Carbon Nanosheets for Near-Infrared Imaging-Guided Combined Photo-Chemotherapy.

Rational design of metal-free multifunctional therapeutic reagents offers great opportunities for cancer treatment in the clinic. Here, graphitic carbon nitride (g-C3N4) quantum dots embedded in carbon nanosheets (CNQD-CN) are in situ prepared via a one-pot hydrothermal approach with formamide as carbon and nitrogen source. The CNQD-CN not only serves as an excellent near-infrared (NIR) fluorescent marker but also acts as a pH-responsive nanocarrier. Moreover, the CNQD-CN possesses both light-to-heat conversion and singlet oxygen generation capabilities under a single NIR excitation wavelength. Further investigations show that systemic delivery of doxorubicin (DOX) using the multifunctional CNQD-CN nanocarrier under NIR irradiation was highly effective to cause cancer cell apoptosis in vitro and inhibit tumor growth in vivo. CNQD-CN represents a multifunctional therapeutic platform for synchronous cancer imaging and treatment through the synergistic effect of phototherapy and chemotherapy.

Efficacy and safety of Bujing Yishi tablet for glaucoma with controlled IOP: study protocol for a multi-centre randomized controlled trial.

BACKGROUND: As an irreversible, intractable disease with vision loss, glaucoma leads to permanent and progressive damage of visual function. Lowering high intraocular pressure (HIOP) is the first choice for treating glaucoma; however, the control of HIOP is not enough to prevent progressive vison loss. Currently, the therapies to treat glaucoma with controlled IOP (GPCI) are unsatisfactory. Chinese medicine is effective for improving visual function in patients with GPCI. Bujing Yishi tablets (BJYSP) have been the standard preparation for treating GPCI in our hospital for decades. However, no rigorous randomized controlled clinical studies have investigated its effects and safety. METHODS: This study will be a 6-month, multicenter, stratified trial following a prospective, randomized, open-label, blinded endpoint (PROBE) protocol. A total of 216 eligible GPCI patients aged 18-75 years will be stratified according to the early, moderate, and advanced stages of glaucoma. After stratifying, the participants will be randomly assigned to the BJYSP group or control group at a ratio of 1:1. Following randomization, participants in the BJYSP group and control group will receive BJYSP and mecobalamin tablets, respectively, for the same 6-month period. The primary outcomes will include the best-corrected visual acuity (BCVA), visual field assessment, visual evoked potential (VEP) test, and Heidelberg retina tomography II (HRT II); the secondary outcomes will include intraocular pressure (IOP) and Traditional Chinese medicine (TCM) clinical symptom scales. The primary and secondary outcomes will be measured at baseline and 8, 16, and 24 weeks thereafter. Safety assessments will also be evaluated at baseline and 12 and 24 weeks thereafter. DISCUSSION: This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of BJYSP as a novel therapeutic strategy for improving visual function in patients with GPCI. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016431. Registered on 1 June 2018.

Magnetic-induced graphene quantum dots for imaging-guided photothermal therapy in the second near-infrared window.

Graphene quantum dots (GQDs) are considered emerging nanomaterials for photothermal therapy (PTT) of cancer due to their good biocompatibility and rapid excretion. However, the optical absorbance of GQDs in shorter wavelengths (<1000 nm) limits their overall therapeutic efficacies as photothermal agent in the second near infrared window (1000-1700 nm, NIR-II). Herein, we report a type of GQDs with strong absorption (1070 nm) in NIR-II region that was synthesized via a one-step solvothermal treatment using phenol as single precursor by tuning the decomposition of hydrogen peroxide under a high magnetic field with an intensity of 9T. The obtained 9T-GQDs demonstrate uniform size distribution (3.6 nm), and tunable fluorescence (quantum yield, 16.67%) and high photothermal conversion efficacy (33.45%). In vitro and in vivo results indicate that 9T-GQDs could efficiently ablate tumor cells and inhibit the tumor growth under NIR-II irradiation. Moreover, the 9T-GQDs exhibited enhanced NIR imaging of tumor in living mice, suggesting the great probability of using 9T-GQDs for in vivo NIR imaging-guided PTT in the NIR-II window.