The clinical application of photothermal therapy (PTT) is severely limited by the tissue penetration depth of excitation light, and enzyme therapy is hampered by its low therapeutic efficiency. As a two-dimensional ultrathin nanosheet with high absorbance in the near-infrared-II (NIR-II) region, the titanium carbide (Ti 3 C 2 ) nanosheet can be used as a substrate to anchor functional components, like nanozymes and nanodrugs. Here, we decorate Pt artificial nanozymes on the Ti 3 C 2 nanosheets to synthesize Ti-based MXene nanocomposites (Ti 3 C 2 T x -Pt-PEG). In the tumor microenvironment, the Pt nanoparticles exhibit peroxidase-like (POD-like) activity, which can in situ catalyze hydrogen peroxide to generate hydroxyl radicals ( • OH) to induce cell apoptosis and necrosis. Meanwhile, the composite shows a desirable photothermal effect upon NIR-II light irradiation with a low power density (0.75 W cm −2 ). Especially, the POD-like activity is significantly enhanced by the elevated temperature arising from the photothermal effect of Ti 3 C 2 T x . Therefore, satisfactory synergistic PTT/enzyme therapy has been accomplished, accompanied by an applicable photoacoustic imaging capability to monitor and guide the therapeutic process. This work may provide an approach for hyperthermia-amplified nanozyme catalytic therapy, especially based on metal catalysts and MXene nanocomposites. KEYWORDS: Ti 3 C 2 T x MXene, platinum nanoparticles, NIR-II light, photothermal, nanozyme
The exploration of single cells reveals cell heterogeneity and biological principle of cellular metabolism. Although a number of mass spectrometry (MS) based single cell MS (SCMS) techniques have been dedicatedly developed with high efficiency and sensitivity, limitations still exist. In this work, we introduced a microscale multifunctional device, the T-probe, which integrates cellular contents extraction and immediate ionization, to implement online in situ SCMS analysis at ambient conditions with minimal sample preparation. With high sensitivity and reproducibility, the T-probe was employed for MS analysis of single HeLa cells under control and anticancer drug treatment conditions. Intracellular species and xenobiotic metabolites were detected, and changes of cellular metabolic profiles induced by drug treatment were measured. Combining SCMS experiments with statistical data analyses, including Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) and two-sample t-test, we provided biological insights into cellular metabolic response to drug treatment. Online MS/MS analysis was conducted at single cell level to identify species of interest, including endogenous metabolites and the drug compound. Using the T-probe SCMS technique combined with comprehensive data analyses, we provide an approach to understanding cellular metabolism and evaluate chemotherapies at the single cell level.
The high-resistive grain boundaries are the bottleneck for Li
+
transport in Li
7
La
3
Zr
2
O
12
(LLZO) solid electrolytes. Herein, high-conductive LLZO thin films with cubic phase and amorphous domains between crystalline grains are prepared, via annealing the repetitive LLZO/Li
2
CO
3
/Ga
2
O
3
multi-nanolayers at 600 °C for 2 h. The amorphous domains may provide additional vacant sites for Li
+
, and thus relax the accumulation of Li
+
at grain boundaries. The significantly improved ionic conductivity across grain boundaries demonstrates that the high energy barrier for Li
+
migration caused by space charge layer is effectively reduced. Benefiting from the Li
+
transport paths with low energy barriers, the presented LLZO thin film exhibits a cutting-edge value of ionic conductivity as high as 6.36 × 10
−4
S/cm, which is promising for applications in thin film lithium batteries.
MicroRNAs (miRNAs) are a class of small non‑coding single‑stranded RNAs that regulate gene expression at the posttranscriptional level. Since the identification of miRNA, accumulating research has shown their involvement in numerous biological processes, including timing of developmental patterning, embryogenesis, cell differentiation, organogenesis, growth control and pathogenesis of human diseases. It is estimated that >30% human genes may be regulated by miRNA, and that each miRNA can regulate >100 target mRNAs. The widespread and distinct expression pattern of miRNAs in normal and disease states has been extensively investigated in the context of human diseases. Due to the diversity of targets, it is challenging to identify the specific target genes and elucidate the biological function of a certain miRNAs. In the present study, it was confirmed that SMAD7 is a direct target of miR‑21, and overexpression of miR‑21 may inhibit the proliferation of rat renal tubular epithelial cells. These findings confirm the results of previous studies, which have demonstrated that miR‑21 regulates the expression of SMAD7 protein. However, further investigation is required to determine whether miR‑21 is involved in renal development and disease, particularly diabetic nephropathy.
Semimetallic nanomaterials as photothermal agents for bioimaging and cancer therapy have attracted tremendous interest. However, the poor photothermal stability, low biocompatibility, and single component limit their therapeutic efficiency in cancer treatment. Here, manganesedoped VSe 2 semimetallic nanosheets were prepared and subsequently modified with chitosan (named VSe 2 /Mn-CS NSs) for combined enzyme catalytic and photothermal therapy. VSe 2 /Mn-CS NSs show high photothermal property with a photothermal conversion efficiency of 34.61% upon 808 nm near-infrared laser irradiation. In the tumor microenvironment, VSe 2 /Mn-CS NSs can convert endogenous H 2 O 2 into lethal hydroxyl radicals (•OH) to induce cancer cell apoptosis. The interaction between glutathione (GSH) and Se−Se bonds in VSe 2 /Mn-CS NSs results in the depletion of GSH level, and the valence states transition of manganese ions is also beneficial for the GSH consumption. This dual depletion of GSH markedly enhances the peroxidase (POD) activity, leading to the high •OH production and the improved therapeutic effect. What is more, the T 1 -weighted magnetic resonance and photoacoustic imaging endow VSe 2 /Mn-CS NSs with the ability to guide and track the treatment process. Our study provides a research strategy for the application of semimetallic nanomaterials in cancer diagnosis and treatment.
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