Carbon-Encapsulated Magnetite Nanodoughnut as a NIR-II Responsive Nanozyme for Synergistic Chemodynamic-Photothermal Therapy.

Magnetite-based nanozymes have attracted great interest for catalytic cancer therapy enabled by catalyzing hydrogen peroxide (H2 O2 ) to produce highly toxic hydroxyl radicals (•OH) to kill tumor cells. However, their therapeutic efficacies remain low due to insufficient •OH. Here, a light-responsive carbon-encapsulated magnetite nanodoughnuts (CEMNDs) with dual-catalytic activities for photothermal-enhanced chemodynamic therapy (CDT) is reported. The CEMNDs can accumulate in tumor and get into tumor cells and effectively act as peroxidase to convert H2 O2 to •OH that causes tumor cell death. The CEMNDs also possess intrinsic glutathione oxidase-like activity that which catalyzes the oxidation of reduced glutathione and produce lipid peroxidase for enhanced catalytic therapy. Furthermore, the CEMNDs can absorb 1064 nm light to elevate local temperature and increase release of Fe ions for photothermal therapy and enhanced CDT respectively. The in vivo experiments in an aggressive and drug-resistant metastatic mouse model of triple negative breast cancer model demonstrate excellent synergistic anti-tumor function and no measurable systemic toxicity of CEMNDs.

Hydrophobic Carbon Dots Derived from Organic Pollutants and Applications in NIR Anticounterfeiting and Bioimaging.

In an effort to fulfill the strategy of sustainable development, Rhodamine B, a common and toxic organic pollutant in the textile industry, was reported for the first time as a single precursor to develop a kind of novel hydrophobic nitrogen-doped carbon dot (HNCD) through a green and facile one-pot solvothermal method. The HNCDs with an average size of 3.6 nm possess left and right water contact angles of 109.56° and 110.34°, respectively. The HNCDs manifest excitation wavelength-tunable and upconverted fluorescence from the ultraviolet (UV) to the near-infrared (NIR) range. Furthermore, the PEGylation of HNCDs enables them to be used as an optical marker for cell and in vivo imaging. Notably, the HNCDs with solvent-dependent fluorescence can be used for invisible inks with a wide range of light responses from UV-vis-NIR spectra. This work not only provides an innovative way to recycle chemical waste but also expands the potential application of HNCDs in NIR security printing and bioimaging.

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.

Hollow Cuprous Oxide@Nitrogen-Doped Carbon Nanocapsules for Cascade Chemodynamic Therapy.

Cuprous-based nanozymes have demonstrated great potential for cascade chemodynamic therapy (CDT) due to their higher catalytic efficiency and simple reaction conditions. Here, hollow cuprous oxide@nitrogen-doped carbon (HCONC) dual-shell structures are designed as nanozymes for CDT oncotherapy. This HCONC with a size distribution of 130 nm is synthesized by a one-step hydrothermal method using cupric nitrate and dimethyl formamide as precursors. The thin-layer carbon (1.88 nm) of HCONC enhances the water-stability and reduces the systemic toxicity of cuprous oxide nanocrystals. The dissolved Cu+ of HCONC in acid solution induces a Fenton-like reaction and exhibits a fast reaction rate for catalyzing H2 O2 into highly toxic hydroxyl radicals (·OH). Meanwhile, the formed Cu+ consumes oversaturated glutathione (GSH) to avoid its destruction of ROS at the intracellular level. In general, both cellular and animal experiments show that HCONC demonstrates excellent antitumor ability without causing significant systemic toxicity, which may present tremendous potential for clinical cancer therapy.

Missed hearing loss in tinnitus patients with normal audiograms.

The prevalence of tinnitus is positively correlated with hearing loss, although, tinnitus can also present alongside clinically normal pure-tone thresholds. As standard pure tone audiograms (PTA) only sample at octave or inter-octaves, they potentially can miss lesions between the tested frequencies. Here we investigate if tinnitus patients with normal audiograms have hearing loss missed by standard PTA testing, referred as "missed hearing loss" in the paper. Hearing thresholds in 106 tinnitus patients who have a normal PTA were tested using fine frequency resolution (1/24 octave step) audiometry, referred as precision PTA (P-PTA), at ±1/3 octave band centered at their tinnitus frequencies. Tinnitus pitch, loudness and residual inhibition were evaluated based on the result of P-PTA. DPOAEs were also tested to evaluate the function of outer hair cells (OHC). Using the P-PTA test, we found that 49% (52 out of 106) of tinnitus patients with normal audiograms showed sharply notched hearing loss and most of the notches were at their tinnitus frequencies. Using a fine frequency step (1/24 octave) to assess tinnitus pitch, the successful matching rate increased to 84%, significantly higher than the rate measured in traditional method (51%, Fisher's test, P < 0.0001, n = 106). The number of patients whose tinnitus loudness was less than 5 dB SL increased from 26% to 55% after the loudness reassessment based on the tinnitus pitch match (n = 106, Chi-Square test, P < 0.01). The percentage of patients who showed positive residual inhibition of tinnitus also increased from 31% to 54% (Chi-Square test, P < 0.05). DPOAEs revealed significantly reduced OAE amplitude in the tinnitus patients, suggesting that OHC dysfunction may contribute to their notched hearing loss. However, in 13 out of 31 patients with notched hearing loss, their DPOAE did not show any reduction which suggests that their notched hearing loss may be induced by the dysfunction of the inner hair cells or afferent synapses (synaptopathy). Our study confirmed hidden cochlear impairments in tinnitus patients with seemingly normal audiograms. We conclude that P-PTA can help identify a mild hearing impairment that may otherwise be missed by conventional PTA and that P-PTA can also improve tinnitus evaluation accuracy.

miR-144-3p, a tumor suppressive microRNA targeting ETS-1 in laryngeal squamous cell carcinoma.

Regional lymph node metastasis and distant metastasis are critical in the prognosis of laryngeal squamous cell carcinoma (LSCC). This study investigated the roles of miR-144-3p and E26 transformation specific-1 (ETS-1) in the invasion and migration of LSCC cells. The effects of miR-144-3p and ETS-1 on FaDu and Hep2 cell growth, migration and invasion were determined. Suppression of ETS-1 by miR-144-3p was confirmed using luciferase assays; the effects of ETS-1 silencing were determined using a xenograft tumor model. The expression of ETS-1 was analyzed in 71 paraffin-embedded tissue biopsies and eight fresh frozen biopsies obtained from LSCC patients. miR-144-3p inhibited the growth, invasion and migration of FaDu and Hep2 cells in part through suppression of epithelial-mesenchymal transition as determined by increased E-cadherin and α-catenin and reduced fibronectin and vimentin expression. Additionally, ETS-1 is a molecular target of miR-144-3p, and silencing ETS-1 expression inhibited FaDu and Hep2 cell invasion and migration as well as reduced Hep2 xenograft tumor volume. In LSCC, the expression of ETS-1 is upregulated with disease progression, and higher ETS-1 expression, which was negatively associated with miR-144-3p levels, adversely corresponded with prognoses. Thus, upregulated ETS-1 levels may promote LSCC metastasis, resulting in poor patient prognosis.

Micro-ribonucleic acid expression profiling and bioinformatic target gene analyses in laryngeal carcinoma.

Abnormal expression of micro-ribonucleic acid (miRNA) might be clinically valuable as a biomarker or treatment target in the early diagnosis, treatment, and prognosis of tumors. However, little is known concerning abnormal miRNA expression of laryngeal carcinoma, one of the most commonly encountered head and neck tumors. Microarray analysis was used to obtain miRNA-expression profiles of ten pairs of freshly frozen laryngeal carcinoma tissue and surrounding normal tissue specimens. Characteristic miRNAs that were significantly related to laryngeal carcinoma were identified. Verification was performed using an additional 32 pairs of samples. The expression of two miRNAs (miR-21-3p and miR-106b-3p) was upregulated in both microarray and quantitative real-time polymerase chain-reaction analyses, whereas the expression of six miRNAs (let-7f-5p, miR-10a-5p, miR-125a-5p, miR-144-3p, miR-195-5p, and miR-203) was downregulated. The decreased expression of let-7f-5p and miR-195-5p is a novel finding in head and neck cancer. The target genes of these miRNAs were also predicted through multiple software programs. The differential expression of miRNAs might be related to the early onset and development of laryngeal carcinoma, and may be exploited as new biomarkers and therapeutic targets in the treatment of laryngeal carcinoma.