Atherosclerosis (AS) progression is driven by multiple interconnected pathological mechanisms. Among them, vascular senescence is both a key accelerator and consequence, interacting with other processes to promote AS development. Traditional monotherapies were limited to achieve synergistic therapeutic effects due to low oral bioavailability and insufficient multi-target efficacy. To overcome these limitations, we developed a baicalein-copper network (Cu-MON) for oral delivery of atorvastatin (ATV), forming a synergistic therapeutic system (CMA). Cu-MON significantly prolonged the gastrointestinal residence and increased the oral bioavailability of ATV without requiring additional excipients. Crucially, Cu-MON regulated senescence-associated genes, enhanced DNA repair pathways, and mitigated DNA damage, effectively counteracting vascular aging. The integrated CMA system combined enzymatic and non-enzymatic dual antioxidant systems to scavenge multiple ROS species. Furthermore, CMA reprogrammed macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotypes, modulated the PPAR-γ/LXR-α/ABCA-1 pathway to enhance cholesterol efflux, inhibited foam cell formation, and regulated hepatic and systemic cholesterol homeostasis. In ApoE−/− mice, CMA markedly reduced aortic plaque burden and fibrosis, while Cu-MON attenuated key features of AS, including decreased ROS, inflammation, DNA damage, and cellular senescence. The CMA demonstrates high synergistic efficacy and biosafety, offering a novel multi-target oral drug strategy for AS treatment.

Mesenchymal stromal cells (MSCs) are multipotent cells of mesodermal origin capable of self-renewal and multilineage differentiation. Characterized by low immunogenicity and tropism toward injury sites, MSCs exhibit critical properties including hematopoietic support, immunomodulation, and tissue regeneration. These unique attributes position MSCs as promising therapeutic tools for hematologic diseases, where disruption of the bone marrow niche impairs normal hematopoiesis. Co-transplantation of MSCs with hematopoietic stem cells (HSCs) facilitates HSC homing to the bone marrow niche and significantly improves post-transplant hematopoietic reconstitution. Furthermore, MSCs show considerable therapeutic potential in both prophylaxis and management of graftversus- host disease (GVHD), a major complication of allogeneic transplantation. The therapeutic mechanisms of MSCs have evolved from an initial focus on engraftment to a broader understanding of their paracrine actions via the "hit-and-run" mechanism, wherein MSCs exert functions through secreted factors and extracellular vesicles before host clearance. Despite these advances, clinical translation faces significant challenges, including poor homing efficiency, cellular heterogeneity, culture-induced senescence, and vulnerability to inflammatory and oxidative stress. This review summarizes clinical applications of MSCs in aplastic anemia, leukemia, and co-transplantation with HSCs, while critically evaluating the balance between therapeutic efficacy and potential risks. Additionally, we discuss emerging bioengineering strategies designed to overcome current limitations and enhance MSC therapeutic potency for next-generation cell therapies in hematologic diseases.

Gene therapy has demonstrated promising efficacy in the treatment of peripheral arterial disease (PAD). However, conventional cationic lipids used in mRNA lipid nanoparticles (LNPs) lack degradable bonds, which may pose potential toxicity and long-term accumulation risks. Although many ionizable lipids have been designed with degradable ester linkages, the development of fully biodegradable cationic alternatives with favorable safety profiles remains of great interest. To address these limitations, we developed a biodegradable cationic alternative via ring-opening polymerization of epsilon-caprolactone initiated by triethanolamine, forming a threearmed polyester (3s-PCL) with tertiary ammonium groups. Subsequent conjugation with arginine or lysine yielded terminal-functionalized polyesters (3sPA /3sPL) as sustainable substitutes for conventional cationic lipids. In vitro and in vivo studies demonstrated that 3sPA-containing LNPs exhibit higher transfection efficiency than conventional LNPs (e.g., MC3- or DOTAP-based LNPs). Notably, arginine-modified 3sPA-LNPs displayed dual bioactivity: effective reactive oxygen species (ROS) scavenging and nitric oxide (NO) release. When loaded with VEGF mRNA, 3sPA-LNPs synergistically promoted angiogenesis in critical limb ischemia by elevating VEGF expression, reducing inflammation through ROS scavenging, and improving microcirculation via NO release. Collectively, these findings establish 3sPA-LNPs as a potent and safe mRNA delivery platform for critical limb ischemia, offering a promising treatment strategy for regenerative therapy.

Myocardial infarction (MI) generates a pathological microenvironment characterized by ischemia and hypoxia, and this increases mortality and morbidity worldwide. We fabricated p-hydroxyphenylpropionic acid-modified gelatin (GTN), a dual-responsive system capable of in situ gelation in the presence of hydrogen peroxide (H2O2) or iron ions. This feature enables GTN to cross-link in the infarcted myocardium, where excessive reactive oxygen species (ROS) and iron ions trigger ferroptosis. The successful modification of gelatin was verified, along with its time- and concentration-dependent responsiveness to H2O2 and iron ions in vitro. We further assessed the biocompatibility, ROS-scavenging activity, and cytoprotective effects of GTN in hostile MI microenvironments. Death receptor 5 fusion protein (DR5) was incorporated into the hydrogel to construct DR5@GTN, aiming to alleviate cardiomyocyte apoptosis. In vivo experiments demonstrated that GTN effectively targeted and accumulated in the infarcted region via transglutaminase-mediated recognition, thereby remodeling the pathological microenvironment. DR5@GTN significantly restored cardiac functions, increased the left ventricular ejection fraction, and reduced the infarct size. DR5@GTN attenuated myocardial fibrosis, promoted angiogenesis, suppressed cardiomyocyte apoptosis, decreased ROS levels, and inhibited myocardial hypertrophy. Collectively, DR5@GTN regulated the "ROS-iron-apoptosis" axis with favorable in situ gelation properties, and this represents a promising strategy for myocardial repair by ameliorating the harsh microenvironment following MI. STATEMENT OF SIGNIFICANCE.

The intravenous delivery of mesenchymal stromal cells (MSCs) is often limited by pulmonary entrapment and poor survival under oxidative stress in inflammatory environments. To overcome these challenges, a multifunctional cell-surface engineering strategy driven by the synergistic coordination of polyethylene glycol (PEG), epigallocatechin gallate (EGCG), and magnesium (Mg2+) was adopted in this study. PEG and EGCG were first covalently coupled to form the polymer, PEG-EGCG, in which PEG provides "stealth" shielding, and EGCG facilitates mild membrane insertion and Mg2+ coordination. The resulting PEG-EGCG-Mg complex self-assembled on MSCs, forming a stealth layer and a metal-phenolic network. This P-E-Mg@MSCs design significantly reduced cell adhesion to endothelium and collagen, thereby diminishing pulmonary trapping and leading to increased bone marrow accumulation in a murine model of immune-mediated aplastic anemia (AA). Furthermore, the coating conferred potent antioxidant and anti-inflammatory properties, thereby improving MSC survival under oxidative stress. In AA mice, treatment with P-E-Mg@MSCs restored peripheral blood counts, reduced bone marrow adiposity, and modulated immune imbalance by upregulating regulatory T cells and downregulating cytotoxic CD8+ T cells, thereby outperforming unmodified MSCs. This work presents a versatile coating platform that integrates adhesion inhibition, microenvironment modulation, and metal-ion coordination to enhance the systemic delivery and therapeutic efficacy of MSCs for regenerative and immunomodulatory applications.

Most anti-tumor agents suffer from systemic non-specific distribution and low aggregation in tumors, which not only decreases the therapeutic efficacy, but also causes systemic toxic side effects in the treatments of tumors. In recent years, the rapid development of nanotechnology has brought new ideas for the application of anti-tumor drugs. Nanomedicines, such as liposomes and micelles, can improve drug targeting and prolong systemic circulation time to promote anti-tumor efficacy and reduce toxic side effects. However, conventional micelles bear the risk of instability and premature drug leaking in the blood circulation. We designed a reduction-responsive core-cross-linked micelle PTX@Fmoc-LA-PEG efficiently encapsulating Paclitaxel (PTX) via π-π stacking and hydrophobic interactions of Fmoc and PTX. Moreover, the micelle was further locked based on the cross-linking properties of the disulfide bonds formed by lipoic acid (LA). As expected, the core-cross-linked micelles PTX@Fmoc-LA-PEG remained stable in normal physiological environments, while restoring the normal drug release rate of micelles under the highly reducing environment due to LA unlocking. The blank micelles (Fmoc-LA-PEG) exhibited excellent biocompatibility, while the drug-loaded micelles (PTX@Fmoc-LA-PEG) displayed a remarkable anti-tumor effect in vitro and in vivo experiments. These results suggested that core-cross-linked micelles PTX@Fmoc-LA-PEG have great potential to improve the targeting and stability of anti-tumor drugs.

Salmonella enteritidis is a common foodborne pathogen in nature, which poses a serious threat to human and animal health. Rapid and accurate detection of salmonella enteritidis is an effective way to control its spread, but the traditional colorimetric method is difficult to quantify accurately. We report a simple in situ growth reduction method for the preparation of nanospheres AuNP@PDA@AgMBA with unique colorimetric and Raman properties, which can be visually qualitative while Raman quantitative detection. With AuNPs as the core, the nanosphere is coated with polydopamine to provide a stronger colorimetric signal and reduce the visual limit of detection (LOD). The modification of 4-mercaptobenzoic acid molecules resulted in a strong surface enhanced Raman scattering (SERS) signal. After the target DNA was amplified by recombinant polymerase amplification, the colorimetric and SERS signal were further amplified. The detection process was carried out on the lateral flow strip, and the black strip was formed to achieve qualitative and quantitative analysis. In the concentration range of 3 x 101 to 3 x 105 CFU/mL, the visual LOD was 3 x 101 CFU/mL. The SERS intensity was detected, and there was a good linear relationship between the signal intensity and the logarithmic value of DNA concentration, and the LOD of Raman mode was 1.51 CFU/mL.

Background: Colorectal cancer (CRC) is one of the common malignant tumors. Chemotherapeutic agents represented by doxorubicin (DOX) are common adjuvant therapies for patients with advanced CRC. However, DOX suffers from dose-dependent cardiotoxicity and myelosuppression due to a lack of targeting and specificity, which severely limits its clinical application. Methods: Herein, we constructed a zeolitic imidazolate framework-8 (ZIF-8) modified by a novel peptide (LT peptide) to deliver the chemotherapeutic drug doxorubicin (DOX) for the targeted treatment of CRC. Results: In this study, LT-PEG@DOX@ZIF-8 nanoparticles were prepared by a simple method with suitable particle size and zeta potential, which were also capable of pH-responsive drug release. In vitro assays exhibited that LT-PEG@DOX@ZIF-8 nanoparticles were effectively taken up by C26 cells, significantly inhibited cell proliferation, and induced apoptosis. Furthermore, in mice models with colorectal tumors, LT-PEG@DOX@ZIF-8 nanoparticles also displayed specific tumor aggregation and exerted anti-tumor effects to prolong the survival of the mice. Conclusions: In conclusion, LT-PEG@DOX@ZIF-8 provides a promising strategy for the delivery of DOX to effectively treat CRC.

Feline parvovirus (FPV) causes severe gastroenteritis and leukopenia in cats, with high morbidity and mortality, necessitating a rapid and effective antigen diagnostic test with high sensitivity and specificity. In this study, a diagnostic platform based on a combination of Recombinase-Aided Amplification (RAA) and CRISPR/Cas12a was established for detecting FPV. Cas12a recombinant protein was purified using Nickel-Nitriloacetic Acid resin after heterologous expression in Escherichia coli. The results of RAA-CRISPR/Cas12a can be detected with a fluorescence reader or lateral flow strips (LFS) for on-site detection. The RAA-CRISPR/Cas12a-LFS had a detection limit of 2.1 × 100 copies of recombinant plasmids per reaction, compared with 2.1 × 103 copies for conventional PCR analysis. Furthermore, no cross-reactivity was observed for the RAA-CRISPR/Cas12a assay with feline coronavirus, feline herpesvirus, and feline calicivirus, demonstrating reasonable specificity. Additionally, 43 cat fecal samples with suspected clinical signs were assayed with RAA-CRISPR/Cas12a-LFS and conventional PCR in parallel. The RAA-CRISPR/Cas12a-LFS showed a 100% coincident rate with PCR. In summary, a novel, visual, sensitive, and specific detection assay based on RAA and CRISPR/Cas12a was developed for FPV.

In the original publication [...].

Hydrogels, as hydrophilic polymers with intricate 3D network structures, exhibit remarkable properties such as adhesion and moisture retention, promising broad applications in wound healing. However, the functionality of a single-component hydrogel system remains relatively simplistic, hindering the advancement towards the spatially and temporally controllable functionality of wound dressings. The incorporation of external physical field-responsive nanomaterials (EPFR-NMs) as composite components offers a viable pathway to modify hydrogels, and the strategies of integrating nanoparticles with hydrogels to create functional external physical field-responsive nanocomposite hydrogels (EPFR-NHs) have garnered significant interest among researchers. In this review, we comprehensively summarize the classification and mechanisms of action of EPFR-NMs, along with design strategies for their integration with hydrogels. Furthermore, we examine the detailed roles and mechanisms of EPFR-NHs in facilitating wound healing at various stages, providing direction and guiding principles for the design and clinical application of EPFR-NHs.

Triple-negative breast cancer (TNBC) is the most aggressive and fatal subtype of breast cancer with disappointing treatment and high mortality. Tumor microenvironment (TME) plays an important role in the invasion and metastasis of TNBC through multiple complex processes. Most anti-metastatic therapies only focus on cancer cells themselves or interfering with single factors of the metastasis process, which is often related to poor outcomes. Thus, effective TNBC treatment relies on regulating multiple key metastasis-related aspects of the TME. Herein, a self-targeting Metal-Organic Frameworks (MOFs) nanoplatform (named as MTX-PEG@TPL@ZIF-8) was designed to improve treatment of TNBC through tumor microenvironment remodeling and chemotherapy potentiation. The self-targeting MOF nanoplatform is consist of ZIF-8 nanoparticles loaded triptolide (TPL) and followed by the coating with methotrexate-polyethylene glycol conjugates (MTX-PEG). Due to MTX's affinity for the overexpressed folate receptor on tumor cell surfaces, MTX-PEG@TPL@ZIF-8 enables effective accumulation and deep penetration in the tumor area by an MTX-mediated self-targeting strategy. This MOF nanoplatform could promptly release the medication after penetrating the tumor cell, due to pH-triggered degradation. Its anti-metastasis mechanism is to inhibit tumor invasion and metastasis by down-regulating the expression of Vimentin, MMP-2 and MMP-9 and increasing the expression of E-cadherin, upregulation of cleaved caspase-3 and cleaved caspase-9 protein expression promote the apoptosis of tumor cells, thereby reducing their migration. It also downregulated the expression of VEGF and CD31 protein to inhibit the generation of neovascularization. Overall, these findings suggest the self-targeting MOF nanoplatform offers new insights into the treatment of metastatic TNBC by TME remodeling and potentiating chemotherapy.

The objective of the study is to prepare quaternized chitosan magnetic nanoparticles (ICG@Fe3O4@QCS) loaded with indocyanine green and to investigate their properties. Fe3O4@QCS nanoparticles were prepared by a one-part precipitation method and evaluated for their structure, particle size, morphology, and magnetic responsiveness. ICG@Fe3O4@QCS nanoparticles were prepared by electrostatic adsorption to investigate the properties of ICG@Fe3O4@QCS nanoparticles, such as particle size, zeta potential, encapsulation rate, drug loading, stability, photo- and thermo-conversion efficiencies, degree of release, biosafety, and in vitro antitumor property. Fe3O4@QCS nanoparticles were successfully prepared in the form of short rods with particle sizes around 20–30 nm, positively charged, with basic Fe3O4 skeleton, and possessing specific magnetic responsiveness. ICG@Fe3O4@QCS nanoparticles were successfully prepared, particle size is around 100–150 nm, charged positively, the encapsulation rate is ≥ 90

The clinical utility of paclitaxel (PTX) is constrained by its poor water solubility and systemic cytotoxicity. Prodrugs of PTX can markedly enhance solubility and reduce the cytotoxicity of the parent drug. However, their efficacy is often constrained by the linkage bond's poor suitable cleavability. In this study, PTX was connected with PEG through a peroxyoxalate linkage bond, a responsive chemical bond of hydrogen peroxide (H2O2). The obtained PTX prodrug polymer (PTX-PEG) can self-assemble into micelles with PTX acting as a hydrophobic core (PTX-PEG/MCs). Notably, the peroxyoxalate linkage bond employed in this study can facilitate the release of the parent drug upon stimulation by reactive oxygen species (ROS), resulting in the generation of carbon dioxide and water as the only byproducts. With the method of solvent evaporation, PTX-PEG/MCs were prepared, and their particle sizes, zeta potentials, appearance morphology, and in vitro stability were characterized. The results show that PTX-PEG/MCs have a particle size of 70.8 +/- 1.5 nm and a spherical surface morphology. Also, in an environment of 5 mu M H2O2, PTX-PEG can perform responsive cleavages of peroxyoxalate bonds, producing carbon dioxide and water with no effect on the chemical structure of PTX. In vitro experiments show that PTX-PEG/MCs can be efficiently absorbed by tumor cells within 15 min of drug administration, effectively inhibiting the proliferation of 4T1 cells and promoting their apoptosis. In vivo distribution experiments show that fast passive-targeting accumulation of PTX-PEG/MCs can be achieved in mouse tumor tissues. Furthermore, in vivo antitumor experiments demonstrate the potential of PTX-PEG/MCs in inhibiting tumor growth and metastasis and their relatively high biosafety. These research results described above show that PTX-PEG/MCs present the characteristics of H2O2-responsive drug release, which provides a strategy for preparing responsive nanodelivery carriers in a ROS microenvironment of tumors.

Industrial wastewater, a byproduct of rapid industrialization, often contains hazardous heavy metal ions such as Cu2+, Cr3+, posing significant risks to environmental and human health. To address the urgent need for fast and simple detection methods in industrial enterprises, we developed gelatin- poly-ε-caprolactone (GEL-PCL) nanofiber fluorescent sensors, incorporating 1,4-dihydroxyanthraquinone (1,4-DHAQ), for the rapid detection of Cu2+, Cr3+ ions. Electrospinning was used to prepare 1,4-DHAQ@GEL-PCL and 1,4-DHAQ/Cu2+@GEL-PCL sensors, leveraging the fluorescence intensity fluctuation behavior between 1,4-DHAQ and the target ions to enable fluorescence-based detection. The sensors were characterized using SEM to confirm nanofiber morphology, and UV–Vis spectroscopy to analyze absorption properties. The sensors demonstrated high sensitivity and selectivity for Cu2+, Cr3+ ions, with detection ranges of 4.8–6.5 × 10−6 M and 2.7–4.3 × 10−6 M, respectively. Furthermore, they maintained stable performance over 6 months of storage and showed reliable results in actual tannery wastewater samples, comparable to ICP-MS data. This study highlights the potential of these sensors as environmentally friendly, cost-effective tools for monitoring heavy metal ion concentrations, offering significant contributions to sustainable industrial wastewater management, and meeting the pressing needs of enterprises for efficient and straightforward monitoring solutions.

Intervertebral disc degeneration (IDD) is a primary contributor to chronic back pain and disability globally, with current therapeutic approaches often proving inadequate due to the complex nature of its pathophysiology. This review assesses the potential of nanoparticle-driven pharmacotherapies to address the intricate challenges presented by IDD. We initially analyze the primary mechanisms driving IDD, with particular emphasis on mitochondrial dysfunction, oxidative stress, and the inflammatory microenvironment, all of which play pivotal roles in disc degeneration. Then, we evaluate the application of metal-phenolic and catalytic nanodots in targeting mitochondrial defects and alleviating oxidative stress within the degenerative disc environment. Additionally, multifunctional and stimuli-responsive nanoparticles are explored for their capacity to provide precise targeting and controlled therapeutic release, offering improved localization and sustained delivery. Finally, we outline future research directions and identify emerging trends in nanoparticle-based therapies, highlighting their potential to significantly advance IDD treatment by overcoming the limitations of conventional therapeutic modalities and enabling more effective, targeted management strategies.

Breast cancer therapy has significantly advanced by targeting the programmed cell death-ligand 1/programmed cell death-1 (PD-L1/PD-1) pathway. BMS-202 (a smallmolecule PD-L1 inhibitor) induces PD-L1 dimerization to block PD-1/PD-L1 interactions, allowing the T-cell-mediated immune response to kill tumor cells. However, immunotherapy alone has limited effects. Clinically approved photodynamic therapy (PDT) activates immunity and selectively targets malignant cells. However, PDT aggravates hypoxia, which may compromise its therapeutic efficacy and promote tumor metastasis. We designed a tumor-specific delivery nanoplatform of liposomes that encapsulate the hypoxia-sensitive antitumor drug tirapazamine (TPZ) and the small-molecule immunosuppressant BMS. New indocyanine green (IR820)-loaded polyethylenimine-folic acid (PEI-FA) was complexed with TPZ and BMS-loaded liposomes via electrostatic interactions to form lipid nanocomposites. This nanoplatform can be triggered by near-infrared irradiation to induce PDT, resulting in a hypoxic tumor environment and activation of the prodrug TPZ to achieve efficient chemotherapy. The in vitro and in vivo studies demonstrated excellent combined PDT, chemotherapy, and immunotherapy effects on the regression of distant tumors and lung metastases, providing a reference method for the preparation of targeted agents for treating breast cancer.

A keloid is a benign tumor manifested as abnormal fibroplasia on the surface of the skin. Curing keloids has become a major clinical challenge, and searching for new treatments and medications has become critical. In this study, we developed a LA67 liposome-loaded thermo-sensitive hydrogel (LA67-RL-Gel) with active targeting for treating keloids via peritumoral injection and explored the anti-keloid mechanism. Firstly, Arg-Gly-Asp (RGD) peptide-modified liposomes (LA67-RL) loaded with LA67 were prepared with a particle size of 105.9 nm and a Zeta potential of −27.4 mV, and an encapsulation efficiency of 89.6 ± 3.7%. We then constructed a thermo-sensitive hydrogel loaded with LA67-RL by poloxamer 407 and 188. The formulation was optimized through the Box–Behnken design, where the impact of the proportion of the ingredients on the quality of the hydrogel was evaluated entirely. The optimal formulation was 20.7% P407 and 2.1% P188, and the gelation time at 37 °C was 9.5 s. LA67-RL-Gel slowly released 92.2 ± 0.8% of LA67 at pH 6.5 PBS for 72 h. LA67-RL-Gel increased adhesion with KF cells; increased uptake; promoted KF cells apoptosis; inhibited cell proliferation; reduced α-SMA content; decreased collagen I, collagen III, and fibronectin deposition; inhibited angiogenesis; and modulated the keloid microenvironment, ultimately exerting anti-keloid effects. In summary, this simple, low-cost, and highly effective anti-keloid liposome hydrogel provides a novel approach for treating keloids and deserves further development.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, linkers and drugs used to construct PDCs, and summarize the clinical applications and challenges of PDC drugs.