Carotid atherosclerotic plaques are a leading cause of ischemic stroke and present a major challenge for early atherosclerosis intervention. Here we engineer a biomimetic delivery platform, such as the Trojan Horse system, composed of platelet membrane and extracellularvesicles (EVs) derived from M2-like macrophages. The resulting vesicles, called platelet-extracellular vesicles (P-EVs), selectively accumulate at injured endothelium and atherosclerotic plaques and enable the co-delivery of PIM1 siRNA and Max-40279. This strategy suppresses endothelial-mesenchymal transition, reduces macrophage foam cell formation, and attenuates inflammatory responses in lesions. In mouse models of atherosclerosis, treatment with P-EVs significantly limits plaque progression. These results establish P-EVs as a targeted approach for modulating vascular inflammation and provide a potential strategy for slowing atherosclerotic plaque development.

Two-dimensional (2D) metal-organic framework (MOF) nanosheets have emerged as a promising class of functional materials. Nevertheless, the fabrication of MOF nanosheets with well-defined uniformity and ultrathin thickness via traditional synthetic strategies still remains a great challenge. Herein, we report that ultrasonic treatment plays a crucial regulatory role in the bottom-up assembly of MOF nanosheets. This innovative synthetic protocol enables the precise preparation of Co-Mn-TCPP nanosheets with a uniform thickness of ∼1.82 nm. Notably, the as-synthesized Co-Mn-TCPP nanosheets exhibit an ultrahigh longitudinal relaxivity (r1) of 12.05 mM-1s-1. A combination of theoretical calculations and experimental characterizations reveals that the exceptional relaxivity of Co-Mn-TCPP nanosheets stems predominantly from their unique 2D square lattice structure, which imposes a strong restriction on molecular motion and thus prolongs the rotational correlation time (τᵣ). Furthermore, this single-unit-cell 2D MOF demonstrates remarkable magnetic resonance imaging (MRI) contrast enhancement efficacy across multiple tumor models. More importantly, it can effectively assist in MRI-guided precise resection of small tumors. This work not only showcases the great versatility of ultrasound as a powerful tool for the synthesis of high-quality MOF nanosheets but also provides a new strategy for the design of high-relaxivity MRI contrast agents by capitalizing on specific 2D topological features.

Magnetic resonance imaging (MRI) often employs contrast agents (CAs) to improve the visualization of lesions. Although iron-based oxides have been clinically approved as T2 CAs, various obstacles have hindered their widespread commercial use. Consequently, there is a pressing demand for innovative T2-type CAs. Herein, we synthesized an iron-based hydrogen-bonded organic framework (Fe-HOF) from Fe-TCPP and explored its potential as a T2-weighted MRI CA. The Fe-HOF demonstrated a superior relaxivity (r2) of 32.067 mM-1 s-1 and a higher r2/r1 ratio of 45.25 compared to Fe-TCPP. This enhancement may be attributed to the combination of the single-atom form of Fe3+ with its increased radius. Our findings indicate that a 6 μmol [Fe]/kg dose of Fe-HOF significantly improves lesion contrast in T2-weighted MRI scans of subcutaneous tumor model mice and liver metastasis model mice of breast tumor. The simplicity of Fe-HOF' s structure ensures the absence of complex metal ions or ligands during synthesis, and the iron component can be metabolized into the endogenous iron pool, resulting in remarkable biocompatibility and biosafety. These findings pave the way for the design of novel T2-weighted MRI probes tailored for cancer characterization at various stages.

Diabetic foot ulcer is a common and serious complication of diabetes, with a high risk of amputation, recurrence, and mortality. Aiming at the characteristics of diabetic wounds and based on the result of network pharmacology, a tailored ligand cyanidin-3-O-glucoside (C3G) was selected to construct a metal-phenolic network (CM) through the self-assembly reaction with manganese ions. CM integrates the pharmacological advantages of C3G in antidiabetes and the anti-inflammatory activity of metal-phenolic networks by simulating the metal coordination structure of antioxidant enzymes. Reasonably, the wound areas of db/db mice with CM treatment rapidly decreased to 3.06% at day 14, accompanied by the improvement of tissue microenvironment. Mechanism investigation indicated that CM can not only reduce inflammation activation and immunoreaction but also increase gene transcripts in glucose metabolism, response to hypoxia, and angiogenesis. It is believed that this work opens a way for designing disease-specific metal-phenolic networks, and the CM with high biosafety promotes the clinical treatment of diabetic wounds.

Magnolol and honokiol are significant phenolic isomers derived from Magnolia officinalis and are considered promising candidates for potent anticancer drugs. A convenient and rapid method for the simultaneous analysis of magnolol and honokiol is essential for investigating their mechanisms of action and pharmacokinetics. In this study, we developed a composite electrode based on a copper-chelated porous coordination network (PCN-224(Cu)) and carbon nanotubes (CNT). Experimental results demonstrated that the PC-CNT/GCE exhibited a substantial redox potential difference (similar to 0.14 V) between magnolol and honokiol under differential pulse voltammetry. The modified electrode enabled the simultaneous detection of both compounds in a mixture, showing a linear increase in response current with detection limits (LOD = 3 sigma/s) of 2.65 mu M for magnolol and 11.4 mu M for honokiol. Additionally, the sensor exhibited sensitivities of 54.894 mu A mM-1 for honokiol and 46.677 mu A mM-1 for magnolol. These findings suggest that PCN-224(Cu)-based electrodes hold great potential for the efficient analysis of phenolic isomers in Magnolia officinalis. Furthermore, this study provides a foundation for new applications of porous coordination networks in electrochemical sensing.

The effectiveness of clinically used magnetic resonance imaging (MRI) contrast agents (CAs) in tumor diagnosis is limited due to their low selectivity and sensitivity. To address this, we propose inactivated cell-based contrast agents (Mn-CCs) by constructing a mineralized tumor cell. Preserving proteins and structures on the cell membrane, Mn-CCs exhibit advantages, including homotypic targeting capabilities, tumor microenvironment (TME)-activated MRI signals, and ultrahigh relaxation rates. Glioma and pancreatic tumor cells were used as model templates to produce Mn-UCs and Mn-SCs. Under TME conditions, the longitudinal relaxation rates of Mn-UCs and Mn-SCs increased to 13.27 and 5.48 mM-1s-1, respectively. In vivo results demonstrated that Mn-UCs showed a superior MRI contrast enhancement in glioma compared to clinically used Gd-DOTA. Furthermore, Mn-SCs specifically enhanced MRI contrast in pancreatic tumors as small as 5.67 ± 1.16 mm3 and enabled clear differentiation between tumor stages. The biosafety, sensitivity, and specificity of Mn-CCs suggest a novel approach for designing biomimetic MRI contrast agents, offering new opportunities for more precise diagnosis of early-stage tumors.

Magnetic resonance imaging (MRI) contrast agents face persistent challenges in achieving target-specific activation and high signal-to-noise ratios (SNRs). To address these limitations, we developed LP-GZF, a bioresponsive nanoprobe leveraging magnetic resonance tuning (MRET) within tumor-targeting liposomes. The system coencapsulates Gd-DOTA (paramagnetic enhancer) and Zn0.4Fe2.6O4@DMSA (superparamagnetic quencher), engineered to switch between "OFF" and "ON" states via spatial separation. It has also been confirmed that the relaxivity of LP-GZF is only related to its state, instead of its concentration. In the native state, the proximity between components suppresses Gd3+ relaxivity (0.15 mM-1 s-1), while the release of Gd-DOTA restores relaxivity to 4.25 mM-1 s-1, a 28.3-fold enhancement. In 4T1 tumor-bearing mice, LP-GZF demonstrated delayed burst-enhancement kinetics, with SNR surging from 29.00 ± 1.13 to 48.88 ± 3.32 at 2 h postinjection, clearly lighting the boundary of tumor tissue. The outstanding performance of LP-GZF is attributed to the selective enrichment in the tumor and the subsequent spatial separation of the "enhancer" and "quencher". The nanoprobe exhibited excellent biocompatibility and hepatorenal clearance. This work establishes a paradigm for stimuli-responsive contrast agents, combining spatiotemporal precision with analytical reliability for early cancer diagnosis.

In the diagnosis of breast cancer, the biggest threat to the women in the world, the range of lesions and the occurrence of lymph node metastasis are the main factors to guide the subsequent treatment. MRI is the main tool for the diagnosis of breast cancer. However, the existing contrast agents are difficult to use in the diagnosis of metastatic breast cancer. To solve this problem, macrophage derived exosomes were utilized to synthesize a responsive MRI contrast agent EVs-M, which have the same membrane structure as the parent cell to achieve passive and active tumor targeting capabilities. The EVs-M can generate a distinct T1 signal from 0.115 mM- 1 s- 1 to 7.642 mM- 1 s- 1 in the tumor microenvironment. In vivo results indicated that EVs-M based MRI successfully identified the primary lesion, metastases lesion and lymph nodes in breast tumor model, and the diagnostic results are completely consistent with pathological findings. In addition, due to its natural composition and structure, the EVs-M has a high biosafety and biocompatibility. This work has proposed a novel strategy to construct MRI contrast agents with high selectivity to tumor, and bring a reliable method for precisely diagnosing metastatic breast cancer.

Accurate determination of cerebral ascorbic acid (AA) is crucial for understanding ischemic stroke (IS) related pathological events. Carbon fiber microelectrodes (CFEs) have proven to be robust tools with high sensitivity toward AA, however, they face ongoing challenges for in situ measurement due to the non-specific adsorption of proteins in brain tissue. In this study, the hydrogen-bonded organic framework PFC-71 is synthesized and modified on CFEs through pi-pi stacking interactions with carboxylated carbon nanotubes (CNT-COOH). It is found that the gating effect and hydrophilicity of PFC-71 provided the CFE with excellent antibiofouling properties. As a result, AA exhibited a low oxidation potential of -30 mV on the CFE/CNT-COOH/PFC-71, even in the presence of 20 mg mL-1 bovine serum albumin. Given the structural advantages of CFE/CNT-COOH/PFC-71, a ratiometric electrochemical strategy for AA is established, enabling the in situ assay of cerebral AA in a middle cerebral artery occlusion (MCAO) model with high accuracy and stability. Hydrogen-bonded organic frameworks (HOFs) are found to improve the antibiofouling property of carbon fiber microelectrodes (CFEs), due to its gating effect and hydrophilicity. On this basis, a ratiometric electrochemical strategy for ascorbic acid (AA) is established, enabling the in situ assay of cerebral AA in a middle cerebral artery occlusion (MCAO) model with high accuracy and stability. image

The hypertrophic scar (HS) is a prevalent cutaneous fibrotic disorder that impacts both the aesthetic and functional aspects of the skin, there is an urgent need for a highly safe and effective approach to address the challenge of HS with thick and deep types. Inspired by the superior deep tissue penetrative ability of near-infrared-II (NIR-II) light and potential mitochondria ROS inducing effect of Chinese medicine lycorine (LYC), we fabricated a Cu2Se@LYC (CL) composite by encapsulating LYC on polyvinyl pyrrolidone (PVP) modified Cu2Se nanoparticles. After NIR-II irradiation, CL could induce the generation of reactive oxygen species (ROS) and mitochondrial damage in hypertrophic scar fibroblasts (HSFs). The subsequent release of cytochrome C (cyt-c) from mitochondria into the cytoplasm and upregulation of beclin1 leads to the activation of endogenous apoptosis and autophagy-mediated cell death. The CL + NIR-II treatment exhibited a pronounced anti-scarring effect in both in vitro and in vivo rabbit ear scar models, leading to a significant reduction in the fibrotic markers including Collagen I/III and α-smooth muscle actin (α-SMA). This study comprehensively investigated the crucial role of HSFs’ autophagy in scar management and proposed a safe and effective therapy based on NIR-II laser for clinical application.

Excessive or persistent inflammation incites cardiomyocytes necrosis by generating reactive oxygen species in myocardial infarction (MI). Hydrogen sulfide (H 2 S), a gaseous signal molecule, can quickly permeate cells and tissues, growing concerned for its cardioprotective effects. However, short resident time and strong side effects greatly restrict its application. Herein, a complex scaffold (AAB) is first developed to slowly release H 2 S for myocardial protection by integrating alginate modified with 2‐aminopyridine‐5‐thiocarboxamide (H 2 S donor) into albumin electrospun fibers. Next, a band‐aid like patch is constructed based on AAB (center) and nanocomposite scaffold which comprises albumin scaffold and black phosphorus nanosheets (BPNSs). With near‐infrared laser (808 nm), thermal energy generated by BPNSs can locally change the molecular structure of fibrous scaffold, thereby attaching patch to the myocardium. In this study, it is also demonstrated that AAB can enhance regenerative M2 macrophage and attenuate inflammatory polarization of macrophages via reduction in intracellular ROS. Eventually, this engineered cardiac patch can relieve inflammation and promote angiogenesis after MI, and thereby recover heart function, providing a promising therapeutic strategy for MI treatment.

Copper ions play a significant role in human bodies, as they are beneficial for many metabolism processes, but excessive Cu2+ may cause various symptoms. Therefore, the development of strategies capable of both sensitive detection and visualization of Cu2+ is greatly important for human health. In this work, a novel ratiometric fluorescence sensor for rapid and visual detection of Cu2+ was designed based on green emission carbon dots (CDs) and red emission CdTe/CdS quantum dots (QDs). We have calculated the chromaticity coordinates of individual CDs and CdTe/CdS QDs, and the chromaticity coordinate of their mixture would change along the line between the two points of CDs and CdTe/CdS QDs in the chromaticity coordinate system. The red fluorescence of QDs can be influenced by Cu2+, and the fluorescence color of CDs-QDs changes from yellow to green as the chromaticity coordinates change with the addition of Cu2+. This traffic-light-type color change was more sensitive to the naked eye compared to conventional single emission-based sensors. This paper not only realized ratiometric fluorescence and visual detection of Cu2+ through a convenient method but also provided a promising strategy of designing an assay kit for trace Cu2+.

The pectin/poly(vinyl alcohol) composite(CoPP) hydrogel was prepared by low frequency oscillation and freezing-thawing.The structure of CoPP hydrogel was characterized by FTIR,DSC,XRD and SEM,the swelling properties were observed,and the diffusion of water and the swelling dynamics were also discussed.The experimental results show that CoPP hydrogel is porous,and has two kinds of crystal regions.The diffusion characteristic index which water molecule immerses into CoPP hydrogel was near 0.5,which indicates the diffusion is in Fick model.The swelling velocity constant of CoPP,the swelling ratio of mass(197.38%~252.49%) and swelling ratio of volume(241.47%~308.93%) of CoPP at the swelling equilibration were superior to those of poly(vinyl alcohol)(PVA) hydrogel.Therefore,the swelling properties of CoPP composite hydrogel are faster and larger,which makes it possible to implant the artificial nucleus pulposus prosthesis in smaller size with the minimally invasive surgery.