Low-intensity pulsed ultrasound improves myocardial ischaemia‒reperfusion injury via migrasome-mediated mitocytosis.

During myocardial ischaemia‒reperfusion injury (MIRI), the accumulation of damaged mitochondria could pose serious threats to the heart. The migrasomes, newly discovered mitocytosis-mediating organelles, selectively remove damaged mitochondria to provide mitochondrial quality control. Here, we utilised low-intensity pulsed ultrasound (LIPUS) on MIRI mice model and demonstrated that LIPUS reduced the infarcted area and improved cardiac dysfunction. Additionally, we found that LIPUS alleviated MIRI-induced mitochondrial dysfunction. We provided new evidence that LIPUS mechanical stimulation facilitated damaged mitochondrial excretion via migrasome-dependent mitocytosis. Inhibition the formation of migrasomes abolished the protective effect of LIPUS on MIRI. Mechanistically, LIPUS induced the formation of migrasomes by evoking the RhoA/Myosin II/F-actin pathway. Meanwhile, F-actin activated YAP nuclear translocation to transcriptionally activate the mitochondrial motor protein KIF5B and Drp1, which are indispensable for LIPUS-induced mitocytosis. These results revealed that LIPUS activates mitocytosis, a migrasome-dependent mitochondrial quality control mechanism, to protect against MIRI, underlining LIPUS as a safe and potentially non-invasive treatment for MIRI.

Low-intensity pulsed ultrasound protects from inflammatory dilated cardiomyopathy through inciting extracellular vesicles.

AIMS: CD4+ T cells are activated during inflammatory dilated cardiomyopathy (iDCM) development to induce immunogenic responses that damage the myocardium. Low-intensity pulsed ultrasound (LIPUS), a novel physiotherapy for cardiovascular diseases, has recently been shown to modulate inflammatory responses. However, its efficacy in iDCM remains unknown. Here, we investigated whether LIPUS could improve the severity of iDCM by orchestrating immune responses and explored its therapeutic mechanisms. METHODS AND RESULTS: In iDCM mice, LIPUS treatment reduced cardiac remodelling and dysfunction. Additionally, CD4+ T cell inflammatory responses were suppressed. LIPUS increased Treg cells while decreasing Th17 cells. LIPUS mechanically stimulates endothelial cells, resulting in increased secretion of extracellular vesicles (EVs), which are taken up by CD4+ T cells and alter their differentiation and metabolic patterns. Moreover, EVs selectively loaded with microRNA (miR)-99a are responsible for the therapeutic effects of LIPUS. The hnRNPA2B1 translocation from the nucleus to the cytoplasm and binding to caveolin-1 and miR-99a confirmed the upstream mechanism of miR-99a transport. This complex is loaded into EVs and taken up by CD4+ T cells, which further suppress mTOR and TRIB2 expression to modulate cellular differentiation. CONCLUSION: Our findings revealed that LIPUS uses an EV-dependent molecular mechanism to protect against iDCM progression. Therefore, LIPUS is a promising new treatment option for iDCM.

Analyte-perturbed balance between reducibility and fluorescence of Ti3C2 MXene quantum dots for label-free, dual-mode detection of silver ions.

BACKGROUND: As an emerging and attractive low-dimensional functional materials, Ti3C2 MXene quantum dots (QDs) enlarge the toolbox of fluorescence sensing. However, monochromatic fluorescence, which only provide one single signal, is often beset by challenges such as false-positive readouts and limitations in selectivity. Consequently, to improve the sensing accuracy by means of cross-verified dual-signal authentication, the endeavor to engineer dual-mode nanoprobes based on Ti3C2 QDs, incorporating both the capability of fluorescence and an alternative sensing mechanism, emerges as a compelling avenue. RESULTS: Here, based on the alterations in colorimetric and fluorescent signals of Ti3C2 QDs with the addition of Ag+, we propose a dual-mode sensor obviating the necessity for nanoprobe labeling. Owing to the decent reducibility of Ti3C2 QDs, Ag+ is adsorbed and reduced, resulting in the generation of plasmonic Ag nanoparticles (NPs), which simultaneously trigger colorimetric responses of the solution and enhance the fluorescent emission of Ti3C2 QDs. The confluence of colorimetry and fluorometry within this strategy optimally harnesses the modulating role of the acquired Ag NPs on the reducing capability and fluorescence characteristics of Ti3C2 QDs. The equilibrium imparts versatility and promising prospects to this analyte-triggered label-free method, which enables a remarkable specificity and an excellent detecting limit (0.45 µM) for Ag+. SIGNIFICANCE: The balance between reducibility and fluorescence of Ti3C2 QDs for dual-mode detection is inventively demonstrated. With the exemplification of a direct influence of both features of the nanoprobe via the introduction of analytes, this study opens the feasibility of the analyte-perturbed felicitous equilibrium, which endows label-free methods with versatility and promising prospects. This design may evoke more biosensing strategies with the function of double-signal mutual verification.

Multi-target responsive nanoprobe with cellular-level accuracy for spatiotemporally selective photodynamic therapy.

Photodynamic therapy is known for its non-invasiveness to significantly reduce undesired side effects on patients. However, the infiltration and invasiveness of tumor growth are still beyond the specificity of traditional light-controlled photodynamic therapy (PDT), which lacks cellular-level accuracy to tumor cells, possibly leading to "off-target" damage to healthy tissues such as the skin or immune cells infiltrated. Here, upconversion nanoparticles (UCNPs) were co-encapsulated with manganese dioxide (MnO2) by amphiphilic polymers poly(styrene-co-methyl acrylate) (PSMA) and further coated with photosensitizer (riboflavin)-loaded mesoporous silica (C@S/V). The C@S/V nanoprobes exhibited shielded upconversion luminescence in normal conditions (pH 7.4, no hydroperoxide (H2O2)) under 980-nm irradiation and thus minimal reactive oxygen production from riboflavin. However, the excess H2O2 (1 mM) and acidic environment (pH 5.5) could decompose the MnO2 within the C@S/V, resulting in remarkable enhancement of upconversion luminescence and a favorable hypoxia-relieving condition for PDT, providing a spatiotemporal signal for therapy initiation. The C@S/V nanoprobes were applied to the co-culture of normal cells (HEK293) and pancreatic cancer cells (Panc02) and performed a selective killing on Panc02 under the 980-nm irradiation. By using the "double-safety" strategy, a responsive C@S/V nanoprobe was designed by the selective activation of acidic and H2O2-rich conditions and 980-nm irradiation for spatiotemporally selective photodynamic therapy with cellular-level accuracy.

Engineering a polymer-encapsulated manganese dioxide/upconversion nanoprobe for FRET-based hydrogen peroxide detection.

Hydrogen peroxide (H2O2) is considered a significant biomarker in various diseases and could induce deleterious health problems at irregular physiological concentrations. Therefore, developing a simple, efficient biocompatible nanoprobe for trace amount H2O2 detection with high sensitivity and specificity is of great help for early diagnosis and therapeutics. Herein, we designed amphiphilic poly(styrene-co-maleic anhydride) (PMSA)-encapsulated nanoclusters composed of upconversion nanoparticles (UCNPs) and manganese dioxide nanoparticles (MnO2 NPs) at a specific ratio to produce a near-infrared (NIR) excited luminescent nanoprobe for H2O2 detection. Our results revealed that the MnO2 NPs tended to experience catalytic decomposition when exposed to H2O2, while the UCNPs were retained inside the PSMA encapsulation, causing recovery of the UCNP emission band at 470 nm in accordance with H2O2 concentration. This luminescence recovery was linearly dependent on H2O2 concentrations, yielding a limit of detection (LOD) of 20 nM. The easy-to-interpret H2O2 nanoprobe also proved high selectivity in the presence of other interfering substances, and biocompatibility and water-dispersibility, making it an ideal candidate for real-time detection of disease-related H2O2 in living organisms.

Excitation energy mediated cross-relaxation for tunable upconversion luminescence from a single lanthanide ion.

Precise control of energy migration between sensitizer ions and activator ions in lanthanide-doped upconversion nanoparticles (UCNPs) nowadays has been extensively investigated to achieve efficient photon upconversion. However, these UCNPs generally emit blue, green or red light only under fixed excitation conditions. In this work, regulation of the photon transition process between different energy levels of a single activator ion to obtain tunable upconversion fluorescence under different excitation conditions is achieved by introducing a modulator ion. The cross-relaxation process between modulator ion and activator ion can be controlled to generate tunable luminescence from the same lanthanide activator ion under excitation at different wavelengths or with different laser power density and pulse frequency. This strategy has been tested and proven effective in two different nanocrystal systems and its usefulness has been demonstrated for high-level optical encryption.

ZIF-8 encapsulated upconversion nanoprobes to evaluate pH variations in food spoilage.

A novel nanoassembly was constructed through encapsulating upconversion nanoparticles (UCNPs) into a metal-organic framework structure (ZIF-8), in which doxorubicin (DOX) was absorbed into pores of ZIF-8. The blue emission of UCNPs was quenched by DOX through the fluorescence resonance energy transfer (FRET) strategy. When the nanoprobe was exposed to food samples with different pH values, ZIF-8 collapsed to release DOX molecules, resulting in upconversion recovery. The porous structure of ZIF-8 provides abundant space for DOX absorption, which significantly improves the detection capacities and accuracy. It is shown that the probe has a good linear relationship when pH values vary from 2.5 to 7.4, and can distinguish pH variations as low as 0.5 in real samples. This strategy has been successfully used to determine food spoilage by determination of pH variations.

Luminescence Nanoprobe in the Near-Infrared-II Window for Ultrasensitive Detection of Hypochlorite.

Sensitive and selective detection of hypochlorite is in great demand for food safety, especially in fresh cold chain products. However, the detection limit of traditional visible emission-based strategies cannot satisfy the requirement of ultrasensitive analysis in practical applications. In this work, we explored a novel luminescent nanoprobe in the near-infrared-II (NIR-II) window to greatly improve the hypochlorite detection limit for analysis of real milk samples, which was based on the fluorescence resonance energy-transfer process between the hypochlorite-responsive dye (FD1080) and the lanthanide-doped downconverted nanoparticles. Specifically, the NIR-II luminescence from Yb ions was first suppressed by FD1080 due to the energy-transfer mechanism. In the presence of hypochlorite, FD1080 was bleached to recover the luminescence. As a proof-of-concept, the optimal nanoprobe exhibited a linear luminescence recovery in the range of 0.1-1 nM with the detection limit of 0.0295 nM for hypochlorite. Real milk sample detection experiments showed that the probe had good accuracy and precision.