Tendon injuries significantly impact quality of life, prompting the exploration of innovative solutions beyond conventional surgery. Extracellular Vesicles (EVs) have emerged as a promising strategy to enhance tendon regeneration. In this study, human Tendon Stem/Progenitor Cells (TSPCs) were isolated from surgical biopsies and cultured in a Growth-Differentiation Factor-5-supplemented medium to promote tenogenic differentiation under static and dynamic conditions using a custom-made perfusion bioreactor. Once at 80% confluence, cells were transitioned to a serum-free medium for conditioned media collection. Ultracentrifugation revealed the presence of vesicles with a 106 particles/mL concentration and sub-200nm diameter size. Dynamic culture yielded a 3-fold increase in EV protein content compared to static culture, as confirmed by Western-blot analysis. Differences in surface marker expression were also shown by flow cytometric analysis. Data suggest that we efficiently developed a protocol for extracting EVs from human TSPCs, particularly under dynamic conditions. This approach enhances EV protein content, offering potential therapeutic benefits for tendon regeneration. However, further research is needed to fully understand the role of EVs in tendon regeneration.

Klebsiella pneumoniae is a gram-negative pathogen that can cause multiple diseases including sepsis, urinary tract infections, and pneumonia. The escalating detections of hypervirulent and antibiotic-resistant isolates are giving rise to growing public concerns. Outer membrane vesicles (OMVs) are spherical vesicles containing bioactive substances including lipopolysaccharides, peptidoglycans, periplasmic and cytoplasmic proteins, and nucleic acids. Emerging studies have reported various roles of OMVs in bacterial virulence, antibiotic resistance, stress adaptation, and host interactions, whereas knowledge on their roles in K. pneumoniae is currently unclear. In this review, we summarized recent progress on the biogenesis, components, and biological function of K. pneumoniae OMVs, the impact and action mechanism in virulence, antibiotic resistance, and host immune response. We also deliberated on the potential of K. pneumoniae OMVs in vaccine development, as diagnostic biomarkers, and as drug nanocarriers. In conclusion, K. pneumoniae OMVs hold great promise in the prevention and control of infectious diseases, which merits further investigation.

Diabetic foot ulcers (DFU), a severe complication of diabetes mellitus, present a global healthcare challenge due to high risks of limb amputation and mortality. This study developed a multifunctional hydrogel dressing, Gelatin Methacryloyl (GelMA) hydrogel loaded with interleukin-4 (IL-4)-engineered exosomes (Exos), designed to synergistically modulate immune responses and enhance angiogenesis for complete diabetic wound repair. The programmed death-ligand 1 (PD-L1)-enriched Exos were engineered via IL-4 overexpression in NIH3T3 fibroblasts. The GelMA hydrogel loaded NIH3T3 fibroblast-derived Exos with IL-4 overexpression (GelMA/ExosIL-4 hydrogel) exhibited favorable physicochemical characteristics, including a three-dimensional porous microstructure, injectability, tissue adhesion, self-healing properties, and sustained moisture retention. In vitro evaluation demonstrated biocompatibility, sustained exosome release, and enhanced viability, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). In a diabetic wound model, the hydrogel significantly accelerated wound closure, promoted re-epithelialization and angiogenesis, and skewed macrophages toward anti-inflammatory M2 polarization while suppressing T-cell proliferation. These findings highlight the dual immunomodulatory and pro-angiogenic efficacy of GelMA/ExosIL-4 hydrogel, offering a promising therapeutic strategy for chronic wound management.

Detection of protein profiling on exosomes exhibits great promise for early non-invasive and accurate diagnosis of tumor in clinical diagnostics. However, it still faces multiple challenges, such as expensive instruments requirement and weak specificity by single biomarker. Herein, based on a dual-recognition strategy, a ternary hybrid of a trigger DNA (TDNA), EpCAM aptamer, and CD63 aptamer was used to capture A549 cells-derived exosomes to release TDNA, which initiated the trans-cleavage activity of CRISPR/Cas12a to nonspecifically cleave single-stranded DNA (ssNDA) and then resulted in the isolating of ssDNA linked nanozyme of Zr/Fe-CeO2@Ir@CaO2@HA (ZFCIrCH). ZFCIrCH not only achieved H2O2/O2 self-supply, but also possessed high peroxidase-like, oxidase-like, and superoxide dismutase-like activities, thereby generating a sensitive colorimetric signal for A549 cells-derived exosomes detection with a low limit of detection (LOD) of 31 particles/mL. Using a smartphone to analyze colorimetric images, exosome concentration also can be precisely quantified with a LOD of 29 particles/mL, which could also successfully distinguish healthy people from lung cancer patients. With the advantages of high sensitivity, good specificity, low cost, and convenient on-site detection of tumor-derived exosomes, the present colorimetric sensor has great promise in the accurate diagnosis of diseases.

Extracellular vesicles (EVs) have emerged as promising biomarkers for various diseases. Encapsulating biomolecules reflective of their parental cells, EVs are readily accessible in bodily fluids. The prospect for minimally invasive, repeatable molecular testing has stimulated significant research; however, challenges persist in isolating EVs from complex biological matrices and characterizing their limited molecular cargo. Technical advances have been pursued to address these challenges, producing innovative EV-specific platforms. This review highlights recent technological developments, focusing on EV isolation and molecular detection methodologies. Furthermore, it explores the translation of these laboratory innovations to clinical applications through the analysis of patient samples, providing insights into the potential diagnostic and prognostic utility of EV-based technologies.

In recent years, exosomes versatility has prompted their study in the biomedical field for diagnostic, prognostic, and therapeutic applications. Exosomes are bi-lipid small extracellular vesicles (30-150 nm) secreted by various cell types, containing proteins, lipids, and DNA/RNA. They mediate intercellular communication and can influence multiple human physiological and pathological processes. So far, exosome analysis has revealed their role as promising diagnostic tools for human pathologies. Concurrently, artificial intelligence (AI) has revolutionised multiple sectors, including medicine, owing to its ability to analyse large datasets and identify complex patterns. The combination of exosome analysis with AI processing has displayed a novel diagnostic approach for cancer and other diseases. This review explores the current applications and prospects of the combined use of exosomes and AI in medicine. Firstly, we provide a biological overview of exosomes and their relevance in cancer biology. Then we explored exosome isolation techniques and Raman spectroscopy/SERS analysis. Finally, we present a summarised essential guide of AI methods for non-experts, emphasising the advancements made in AI applications for exosome characterisation and profiling in oncology research, as well as in other human diseases.

Extracellular vesicles (EVs) are nanoscale, membrane-bound structures secreted by various cell types into biofluids. They show great potential as biomarkers for disease diagnostics, owing to their ability to carry molecular cargo that reflects their cellular origin. However, the inherent heterogeneity of EVs in terms of size, composition, and source presents significant challenges for reliable detection and analysis. Recent advances in bioreceptor-based biosensor technologies provide promising solutions by offering high sensitivity and specificity in EV detection and characterization. These technologies address the limitations of conventional methods, such as ultracentrifugation and bulk analysis. Biosensors utilizing antibodies, aptamers, peptides, lectins, and molecularly imprinted polymers enable precise detection of EV subpopulations by targeting specific EV surface markers, including proteins, lipids, and glycans. Additionally, these biosensors support multiplexed and real-time analysis while preserving the structural integrity of EVs. This review highlights the transformative potential of combining modern biosensing tools with bioreceptor technologies to advance EV research and diagnostics, paving the way for innovations in disease diagnostics and therapeutic monitoring.

Exosomes are extracellular vesicles that received attention for their potential use in the treatment of various injuries. They communicate intercellularly by transferring genetic and bioactive molecules from parent cells. Although exosomes hold immense promise for treating neurodegenerative and oncological diseases, their actual clinical use is very limited because of their biogenesis and secretion. Recent studies have shown that small molecules can significantly enhance exosome biogenesis, thereby remarkably improving yield, functionality, and therapeutic effects. These molecules modulate critical pathways toward optimum exosome production in a mode that is either ESCRT dependent or ESCRT independent. Improved exosome biogenesis may provide new avenues for targeted cancer therapy, neuroprotection in neurodegenerative diseases, and regenerative medicine in wound healing. This review explores the role of small molecules in enhancing exosome biogenesis and secretion, highlights their underlying mechanisms, and discusses emerging clinical applications. By addressing current challenges and focusing on translational opportunities, this study provides a foundation for advancing cell-free therapies in regenerative medicine and beyond.

Extracellular vesicles (EVs) are nanoscale membrane vesicles actively released by cells into a variety of biofluids. EVs carry myriad molecular cargoes; these include classical genetic biomarkers inherited from the parent cells as well as EV modifications by other entities (e.g., small molecule drugs). Aided by these diverse cargoes, EVs enable long-distance intercellular communication and have been directly implicated in various disease pathologies. As such, EVs are being increasingly recognized as a source of valuable biomarkers for minimally-invasive disease diagnostics and prognostics. Despite the clinical potential, EV molecular profiling remains challenging, especially in clinical settings. Due to the nanoscale dimension of EVs as well as the abundance of contaminants in biofluids, conventional EV detection methods have limited resolution, require extensive sample processing and can lose rare biomarkers. To address these challenges, new micro- and nanotechnologies have been developed to discover EV biomarkers and empower clinical applications. In this review, we introduce EV biogenesis for different cargo incorporation, and discuss the use of various EV biomarkers for clinical applications. We also assess different chip-based integrated technologies developed to measure genetic and modified biomarkers in EVs. Finally, we highlight future opportunities in technology development to facilitate the clinical translation of various EV biomarkers.

Protein biomarkers on breast cancer-derived small extracellular vesicles (BC-sEVs) hold great promise in liquid biopsy. However, it remains challenging due to their inherent heterogeneity and low abundance. Herein, we developed an AND logic gate-based DNA cascade signal amplification strategy, termed Alternating Primer Exchange Reaction-activated Cas12a (Alt-PER-Cas12a), for the ultrasensitive detection of BC-sEVs in clinic samples. This dual-protein recognition system employs EpCAM/MUC1-specific capture probes to release two DNA hairpins (Hep and Hmu) as AND gate inputs in Alt-PER. The corresponding Hep and Hmu hairpins can initiate the Alt-PER with a large amount of primers to generate long single-stranded DNA products with alternating repeat units. Each repeating unit serves as a CRISPR activator, inducing the trans-cleavage activity of Cas12a and enabling cascade signal amplification. The as-constructed strategy exhibits excellent sensitivity with LOD of 2.6 × 103 particles/mL. It has been successfully used to discriminate breast cancer patients from healthy donors (AUC = 0.992) in clinical validation, and shows great potential for liquid biopsy.

While primary breast cancer (BC) is often effectively managed, metastasis remains the primary cause of BC-related fatalities. Gaps remain in our understanding of the mechanisms regulating cancer cell organotropism with predilection to specific organs. Unraveling mediators of site-specific metastasis could enhance early detection and enable more tailored interventions. Liquid biopsy represents an innovative approach in cancer involving the analysis of biological materials such as circulating tumor DNA and tumor-derived extracellular vesicles (EV) found in body fluids like blood or urine. This offers valuable insights for characterizing and monitoring tumor genomes to advance personalized medicine in metastatic cancers.

We performed in-depth analyses of EV cargo associated with BC metastasis using eight murine cell line models with distinct metastatic potentials and organotropism to the lung, the bone, the liver, and the brain. We characterized the secretome of these cells to identify unique biomarkers specific to metastatic sites.

Small EVs isolated from all cell lines were quantified and validated for established EV markers. Tracking analysis and electron microscopy revealed EV secretion patterns that differed according to cell line. Cell-free (cf)DNA and EV-associated DNA (EV-DNA) were detected from all cell lines with varying concentrations. We detected a TP53 mutation in both EV-DNA and cfDNA. Mass spectrometry-based proteomics analyses identified 698 EV-associated proteins, which clustered according to metastatic site. This analysis highlighted both common EV signatures and proteins involved in cancer progression and organotropism unique to metastatic cell lines. Among these, 327 significantly differentially enriched proteins were quantified with high confidence levels across BC and metastatic BC cells. We found enrichment of specific integrin receptors in metastatic cancer EVs compared to EVs secreted from non-transformed epithelial cells and matched tumorigenic non-metastatic cells. Pathway analyses revealed that EVs derived from parental cancer cells display a cell adhesion signature and are enriched with proteins involved in cancer signaling pathways.

Taken together, the characterization of EV cargo in a unique model of BC organotropism demonstrated that EV-DNA and EV proteomes were informative of normal and cancer states. This work could help to identify BC biomarkers associated with site-specific metastasis and new therapeutic targets.

The dysfunction of wound-healing processes can result in chronic non-healing wounds and pathological scar formation. Current treatment options often fall short, necessitating innovative approaches. Exosomes, extracellular vesicles secreted by various cells, have emerged as promising therapeutic agents serving as an intercellular communication system. By engineering exosomes, their cargo and surface properties can be tailored to enhance therapeutic efficacy and specificity. Engineered exosomes (eExo) are emerging as a favorable tool for treating non-healing wounds and pathological scars. In this review, we delve into the underlying mechanisms of non-healing wounds and pathological scars, outline the current state of engineering strategies, and explore the clinical potential of eExo based on preclinical and clinical studies. In addition, we address the current challenges and future research directions, including standardization, safety and efficacy assessments, and potential immune responses. In conclusion, eExo hold great promise as a novel therapeutic approach for non-healing wounds and non-healing wounds and pathological scars. Further research and clinical trials are warranted to translate preclinical findings into effective clinical treatments.

Oxidative stress can affect many aspects of the reproduction process. The embryo implantation process is also one of the critical steps in establishing a successful pregnancy, and several factors, including oxidative stress, can impact the process. Oxidative stress is a state of imbalance between pro-oxidant molecules such as reactive oxygen species (ROS) and antioxidant defenses. Excessive levels of ROS cause damage to the cellular macromolecules such as nucleic acids, proteins, and lipids, resulting in cell dysfunction and pathological conditions. Recently, studies have displayed the therapeutic and antioxidant properties of exosomes derived from stem cells. Exosomes are one type of extracellular vesicles (EVs) secreted by almost all cells and contain different biomolecules. The unique properties of exosomes, like regulation of biological processes, transportation of biomolecules, stability, and biodegradability, can make exosomes a promising therapeutic option in reproductive disorders and diseases. Exosomes also can significantly improve the curative effect of oxidative stress-related pathogenesis. Accordingly, this review aims to provide a novel overview of how exosomes derived from stem cells can regulate oxidative stress and support the process of embryo implantation, hoping to pave the way to clinical applications and future research in this field.

Exosomes, a subtype of extracellular vesicles, are increasingly recognized as promising biomarkers for human cancers. Rapid detection and classification of esophageal cancer-associated exosomes could significantly improve non-invasive screening for potential patients. This study aims to establish a label-free, direct surface-enhanced Raman scattering (SERS) method to capture characteristic molecular information from both esophageal cancer cells and their corresponding exosomes using confocal Raman microscopy. The results revealed distinct Raman spectra for esophageal cancer cells and their exosomes within the range of 500-1600 cm-1, with notable signal similarities observed at 506-622, 778-832, 1079-1098, and 1572-1630 cm-1. In contrast, significant differences were identified in Raman peaks related to nucleic acids (723, 654, 1354 cm-1) and proteins (998, 1028, 1354, 1560 cm-1). An orthogonal partial least squares discriminant analysis (OPLS-DA) model was utilized to discern subtle variations among these highly similar samples, achieving an accuracy rate of 100%. By comparing the spectral correlations between esophageal cancer cells and their exosomes, this study provides valuable insights into the molecular composition and cellular origins of exosomes. The findings demonstrate the potential of integrating SERS with OPLS-DA for the precise and rapid detection and monitoring of esophageal cancer through exosomal biomarkers, offering a powerful tool for diagnostic applications.

Liquid biopsy has emerged as a transformative approach for early cancer detection and treatment monitoring, offering significant potential to improve patient outcomes. However, isolating tumor-derived extracellular vesicles (EVs) from body fluids is often impeded by background noise, making subsequent analysis challenging. Herein, a bio-inspired 3D silicon microanemone (SMA) microfluidic chip is reported. This innovative structure is prepared by a two-step lithographic method combined with nanosphere lithography, achieving an impressive isolation efficiency of 89.4%. Simulation results reveal that the hierarchical structure not only provides more antibody binding sites but also synergizes with an integrated chaotic mixer to amplify fluid perturbations, while inducing a flow around circular cylinder phenomenon to enhance EV-antibody interactions. Finally, the SMA chip's performance is assessed with clinical samples and combined with RT-qPCR-based β-actin (ACTB) mRNA quantification in purified EVs. The results demonstrate its high sensitivity and specificity in isolating cancer-related EV subgroups, enabling non-invasive and precise detection of cancer biomarkers in blood samples.

Extracellular vesicles (EVs) are heterogeneous nanoscale membrane vesicles released by almost all cell types into the circulation. Depending on their biogenesis and cells of origin, EVs show considerable heterogeneity in their biophysical and biomolecular composition and can serve as reflective and dynamic blood biomarkers for personalized medicine. Conventional analytical technologies, however, often lack the compatibility to reveal nanoscale EV features and resolve vesicle heterogeneity. The past decade has since witnessed the development of various nanoplasmonic technologies to empower EV analysis, through bulk and single-vesicle characterization, at an unprecedented scale and resolution. These platforms achieve versatile measurements that are not only size-matched to EV dimensions but can also probe multiplexed biomolecular contents, thereby providing new insights into EV heterogeneity and enabling transformative clinical opportunities. In this review, key characteristics of EVs and their remarkable heterogeneity are introduced. The sensing principles of plasmonic platforms are also discussed, with recent technology developments highlighted to resolve EV heterogeneity, through bulk analyses of EV subpopulations as well as high-resolution single-EV measurements. An outlook is further provided on emerging opportunities, at the interface of biomarker discovery and technology innovation, to develop empowering nanoplasmonic EV platforms for personalized medicine. biosensing; bulk analysis; extracellular vesicles; nanoplasmonics; single-vesicle analysis.

Esophageal cancer is a major global health challenge, with high incidence and mortality due to the lack of rapid and sensitive diagnostic tools and specific biomarkers. Cancer-cell-derived extracellular vesicles (EVs) carry unique proteins and nucleic acids, making them valuable sources of cancer biomarkers. We report an integrated method that combines an ultrafast exosome isolation system (EXODUS) with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to detect EVs and identify protein biomarkers for diagnosing and monitoring esophageal squamous cell carcinoma (ESCC). EVs derived from 20 mL culture medium supernatant of ESCC cells with varying degrees of differentiation serve as analysis models. We use EXODUS to isolate EVs rapidly. We then analyze the intact EVs using MALDI-TOF MS, which provides cell line-specific EV fingerprints in minutes. These protein fingerprints allow the discrimination of ESCC from normal control cells and enable the classification of ESCC based on the degree of cell differentiation. We explore critical EV biomarker peaks for ESCC diagnosis (5555 m/z, 8603 m/z, etc.) and monitoring (2268 m/z, etc.). Potential EV biomarker candidates, including YBX1, DIRAS2, HIST1H2AH, and MYBBP1A, are identified through tandem mass tag (TMT) proteomics. We tentatively assign the protein identities of EV marker peaks by correlation with the TMT proteomics. Applying this method to plasma-derived EVs shows promise for rapid, minimally invasive diagnosis and monitoring of ESCC.

Extracellular vesicles (EVs) are membrane-bound nanoparticles (50-1000 nm) secreted by all cell types and play critical roles in various biological processes. Among these, exosomes, a smaller subset of EVs, have attracted considerable interest due to their potential applications in diagnostics and therapeutics. However, conventional EV isolation methods are often limited by inefficiencies in processing time, recovery, and scalability. Hydrophobic interaction chromatography utilizing capillary-channeled polymer (CCP) fiber stationary phases offers a promising alternative, enabling rapid (<15 min), cost-effective (∼$5 per column) EV isolation with high loading capacities (∼1010-10¹² particles) and minimal sample pre-processing. Despite these advantages, achieving high-throughput EV isolation for larger-scale applications using the CCP fiber platform is the present challenge. To this end, further optimization of stationary phase packing and adsorption conditions is necessary to maximize the available binding surface area in the current microbore column format. This study systematically investigates the influence of interstitial fraction (i.e. packing density) in polyester (PET) CCP fiber columns on the dynamic binding capacity (DBC) of EVs isolated from human urine using a high-performance liquid chromatography platform. Microbore columns (0.76 mm i.d. × 300 mm) packed with PET CCP fibers in both an eight-channel (PET-8) and a novel trilobal (PET-Y) configuration were evaluated using breakthrough curves and frontal analysis. The results reveal that lower packing densities correlate with higher mass- and surface area-based EV binding capacities, with a maximum DBCs of 2.86 × 10¹³ EVs g-1 fiber and 1.22 × 10¹⁴ EVs m⁻² fiber achieved in <2 min of sample loading. Under optimum conditions, surface utilization of >50 % is realized. These results establish a framework for optimizing CCP fiber-based platforms to enhance EV capture efficiency, facilitating the development of scalable EV isolation techniques for biomedical research and therapeutic applications.

The isolation and detection of exosomes as tumor markers are of vital importance for the early diagnosis, therapeutic monitoring, and mechanistic studies of tumors. Here, exosomes derived from breast cancer cells were chosen as model targets, and a wash-free, enzyme-free, handheld mini centrifugation method based on hydrogels was developed to effectively isolate and detect breast cancer exosomes. Dual aptamers (CD63-T1 and EpCAM-T2) were employed to specifically recognize and capture breast cancer exosomes. This specific recognition triggered the formation of hybridization chain reaction (HCR) nanostructures on the captured exosomes through the interaction of hairpin 1 and the alginate complex (H1-Alg) and hairpin 2 (H2-Cy3). The interaction of Ca2+ and alginate enabled the in situ formation of a hydrogel on the exosome surface. Subsequent low-speed centrifugation using a handheld mini centrifuge facilitated the efficient isolation of the exosomes, thereby eliminating the need for tedious washing steps. Utilizing the classical chelation reaction of ethylene diamine tetraacetic acid (EDTA) with Ca2+, the hydrogel can be rapidly cleaved for enzyme-free release of exosomes. The method demonstrated excellent capture and release efficiencies of approximately 85% and 98%, respectively, for specific cancerous exosomes. Notably, the exosomes isolated by the hydrogel system retained excellent biological activity, making them suitable for further analysis and potential applications. Meanwhile, the highly sensitive detection of breast cancer exosomes based on this strategy could also be achieved with a lower limit of detection as low as 3.2 × 103 particles/mL. This work provides a novel and cost-effective strategy for the effective isolation and detection of tumor-derived exosomes, which can help to promote the subsequent application of exosomes in research.

Probiotics such as Lactobacillus and Bifidobacterium spp. have been shown to be critical for maintaining host homeostasis. In recent years, key compounds of postbiotics derived from probiotic metabolism and cellular secretion have been identified for their role in maintaining organ immunity and regulating intestinal inflammation. In particular, probiotic-derived extracellular vesicles (PEVs) can act as postbiotics, maintaining almost the same functional activity as probiotics. They also have strong biocompatibility and loading capacity to carry exogenous or parental active molecules to reach distal organs to play their roles. This provides a new direction for understanding the intrinsic microbiota-host communication mechanism. However, most current studies on PEVs are limited to their functional effects/benefits, and their specific physicochemical properties, composition, intrinsic mechanisms for maintaining host homeostasis, and possible threats remain to be explored. Here, we review and summarize the unique physicochemical properties of PEVs and their bioactivities and mechanisms in mediating microbiota-host communication, and elucidate the limitations of the current research on PEVs and their potential application as postbiotics.

Extracellular vesicles (EVs) are promising non-invasive biomarkers for cancer diagnosis. EVs proteins play a critical role in tumor progress and metastasis. However, accurately and reliably diagnosing cancers is greatly limited by single protein marker on EVs. Here, we reported an accurate diagnosis model of gastric cancer by analyzing five types of EVs surface proteins using machine learning in a retrospective study design. A washing-free detection method based on aptasensor and exonuclease Ⅰ was used to profile EVs surface proteins. The aptamer was designed as hairpin structure. The presence of target protein positive EVs converted the conformation of hairpin probes, which subsequently degraded by exonuclease Ⅰ. The exposed target protein could bind with and then open new hairpin probes, thus forming an amplification cycle. The lengths of different detection probes were optimized for detection. With the combination of five target proteins, five machine learning algorithms were compared to achieve a higher diagnostic accuracy. The best model, XGBoost, validated with 20 % of detection results could reach an accuracy of 0.8421. Furthermore, the XGBoost-based surface protein analysis could precisely identify gastric cancer patients with the area under the curve value of 0.9347 (95 % confidential interval (CI) = 0.8590 to 1.000). Since our method utilized a simple and versatile design of detection probes, its diagnostic scope could potentially be expanded to include different protein markers and accurately diagnose other diseases in the future.

Hepatocellular carcinoma (HCC) poses a significant global health burden, with escalating incidence rates and substantial mortality. The predominant etiological factors include liver cirrhosis (LC) and chronic hepatitis B infections (CHB). Surveillance primarily relies on ultrasound and Alpha-fetoprotein (AFP), yet their efficacy, particularly in early HCC detection, is limited. Hence, there is a critical need for accurate non-invasive biomarkers to enhance surveillance and early diagnosis. Extracellular vesicles (EVs) hold promises as stable carriers of signaling molecules, offering potential in tumor diagnosis. Our study developed a novel tidal microfluidic chip for label-free EV isolation, enabling rapid and efficient enrichment from small plasma volumes. Through transcriptome sequencing and single-cell analysis, we identified HMMR and B4GALT2 as promising HCC-associated biomarkers in EVs. In a comprehensive clinical evaluation, bi-mRNAs in EVs exhibited superior diagnostic performance over AFP, particularly in distinguishing early-stage HCC or AFP-negative cases from high-risk individuals (CHB/LC). Notably, our study demonstrated the potential of bi-mRNAs to complement imaging examinations, enabling early detection of HCC lesions. In conclusion, the tidal microfluidic chip offers a practical solution for EV isolation, with the integration of EV-based biomarkers presenting opportunities for improved early detection and management of HCC in clinical practice.

Extracellular vesicles are nanoscale vesicles released by a diversity of cells that mediate intercellular communication by transporting an array of biomolecules. They are gaining increasing attention in cancer research due to their ability to carry specific biomarkers. This characteristic makes them potentially useful for highly sensitive, noninvasive diagnostic procedures and more precise prognostic assessments. Consequently, EVs are emerging as a transformative tool in cancer treatment, facilitating early detection and personalized medicine. Despite significant progress, clinical implementation is hindered by challenges in EV isolation, purification, and characterization. However, developing advanced biosensor technologies offers promising solutions to these obstacles. This review highlights recent progress in biosensors for EV detection and analysis, focusing on various sensing modalities including optical, electrochemical, microfluidic, nanomechanical, and biological sensors. We also explore techniques for EV isolation, characterization, and analysis, such as electron microscopy, atomic force microscopy, nanoparticle tracking analysis, and single-particle analysis. Furthermore, the review critically assesses the challenges associated with EV detection and put forward future directions, aiming to usher in a cutting-edge era of precision medicine through advanced, sensor-based, noninvasive early cancer diagnosis by detecting EV-carried biomarkers.

Surface plasmons, a unique optical phenomenon arising at the interface between metals and dielectrics, have garnered significant interest across fields such as biochemistry, materials science, energy, optics, and nanotechnology. Recently, plasmonics is evolving from a focus on "classical plasmonics," which emphasizes fundamental effects and applications, to "integrative plasmonics," which explores the integration of plasmonics with multidisciplinary technologies. This review explores this evolution, summarizing key developments in this technological shift and offering a timely discussion on the fusion mechanisms, strategies, and applications. First, we examine the integration mechanisms of plasmons within the realm of optics, detailing how fundamental plasmonic effects give rise to optical multi-effects, such as plasmon-phonon coupling, nonlinear optical effects, electromagnetically induced transparency, chirality, nanocavity resonance, and waveguides. Next, we highlight strategies for integrating plasmons with technologies beyond optics, analyzing the processes and benefits of combining plasmonics with acoustics, electronics, and thermonics, including comprehensive plasmonic-electric-acousto-thermal integration. We then review cutting-edge applications in biochemistry (molecular diagnostics), energy (harvesting and catalysis), and informatics (photonic integrated circuits). These applications involve surface-enhanced Raman scattering (SERS), surface-enhanced infrared absorption (SEIRA), surface-enhanced fluorescence (SEF), chirality, nanotweezers, photoacoustic imaging, perovskite solar cells, photocatalysis, photothermal therapy, and triboelectric nanogenerators (TENGs). Finally, we conclude with a forward-looking perspective on the challenges and future of integrative plasmonics, considering advances in mechanisms (quantum effects, spintronics, and topology), materials (Dirac semimetals and hydrogels), technologies (machine learning, edge computing, in-sensor computing, and neuroengineering), and emerging applications (5G, 6G, virtual reality, and point-of-care testing).

The accurate and sensitive detection of tumor-derived exosomes holds significant promise for the early diagnosis of cancer. In this study, an electrochemical aptasensor was developed for the high-performance detection of exosomes by integrating dual-probe recognition and hybridization chain reaction (HCR). A dual-probe recognition unit composed of a MUC1 aptamer (MUC1-Apt) probe and cholesterol probe was designed for capturing target exosomes and reducing the interference from free proteins, significantly improving the accuracy of exosome detection. It should be noted that the dual-probe recognition unit was formed in conjunction with the HCR. Moreover, a large number of biotins were also assembled on the HCR product, which were used to capture avidin-horseradish peroxidase (SA-HRP) for signal amplification. The CD63 aptamer (CD63-Apt) was immobilized on the surface of a gold electrode for specifically capturing exosomes to construct a classical sandwiched structure. The loaded SA-HRP can efficiently catalyze the reaction of 3, 3', 5, 5' tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) to generate a large electrochemical signal. According to this phenomenon, a linear relationship of this proposed aptasensor was achieved between the electrochemical response and 1 × 102-1 × 107 particles/mL exosomes, with a detection limit of 45 particles/mL. Moreover, the aptasensor exhibited accepted stability and potential clinical applicability. All results proved that this aptasensor has a promising application in exosome-based disease diagnostics.

Gastric cancer invades local tissue extensively and metastasizes through the circulation to remote organs. Patients with metastasized gastric cancer have poor clinical outcomes. The vasculature in the cancer niche is developed poorly, thus allowing cancer cells to be released into the circulation. However, it is poorly understood how cancer cells adhere to and transmigrate through the fully developed endothelium in remote organs and what key adhesive ligands are involved in the process. Here, we report results from a study designed to investigate the role of hyperadhesive VWF (von Willebrand factor) in promoting the pulmonary metastasis of gastric cancer.

We used mouse models to investigate the roles of hyperadhesive VWF in the pulmonary metastasis of gastric cancer. The findings from these mouse models were validated through in vitro experiments that specifically examined how VWF promoted gastric cancer-derived extracellular vesicles to activate endothelial cells and analyzed established databases of patients with gastric cancer.

VWF in cancer-bearing mice became hyperadhesive and mediated the adhesion of gastric cancer-derived extracellular vesicles to the endothelium, where gastric cancer-derived extracellular vesicles caused endothelial permeability and promoted the transmigration of cancer cells to the interstitial tissue of the lungs. Reducing VWF adhesive activity by the metalloprotease ADAMTS-13 (A disintegrin and metalloprotease with thrombospondin type motifs, type 13) prevented the pulmonary metastasis of gastric cancer cells in mice. We further validated the findings in mice through targeted in vitro experiments and by associating VWF with the outcomes of patients with gastric cancer through established databases of patients with gastric cancer using bioinformatics tools.

We show how VWF becomes hyperadhesive to promote the pulmonary metastasis of gastric cancer through its interaction with gastric cancer-derived extracellular vesicles and that the hyperadhesive activity of VWF is reduced by ADAMTS-13 to prevent the metastasis.

The diagnosis and exploration of central nervous system (CNS) diseases remain challenging due to the blood-brain barrier (BBB), complex signaling pathways, and heterogeneous clinical manifestations. Neurons, as the core functional units of the CNS, play a pivotal role in CNS disease progression. Extracellular vesicles (EVs), capable of crossing the BBB, facilitate intercellular and cell-extracellular matrix (ECM) communication, making neuron-derived extracellular vesicles (NDEVs) a focal point of research. Recent studies reveal that NDEVs, carrying various bioactive substances, can exert either pathogenic or protective effects in numerous CNS diseases. Additionally, NDEVs show significant potential as biomarkers for CNS diseases. This review summarizes the emerging roles of NDEVs in CNS diseases, including Alzheimer's disease, depression, traumatic brain injury, schizophrenia, ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. It aims to provide a novel perspective on developing therapeutic and diagnostic strategies for CNS diseases through the study of NDEVs.

Exosomes are cell-secreted nanoscale vesicles 30-150 nm in size and encompass a diverse array of biomolecules, including lipids, proteins, and nucleic acids. Exosomes play pivotal roles during the intercellular exchange of materials and information, and are closely associated with the onset and progression of a variety of diseases. Therefore, comprehensively investigating exosomes is very important in terms of disease diagnosis and treatment. However, exosomes are genetically heterogeneous and are composed of different materials. Additionally, exosome-size and packing-specific-biomarker heterogeneities result in biofunction diversity. Moreover, isolating and analyzing exosomes is highly challenging owing to their small sizes and heterogeneities. Accordingly, effective separation methods and analytical techniques for highly specifically and efficiently identifying exosomes are urgently needed in order to better understand their functionalities. While separation and analysis is required to reveal exosome heterogeneity, the former is confronted by three primary challenges. Firstly, exosome heterogeneity (including heterogeneous marker expressions and size heterogeneity that results in heterogeneous functions) results in systems that are very difficult to separate. Secondly, the coexistence of non-vesicular contaminants (lipoprotein nanoparticles, soluble proteins, nucleic acids, etc.) and the complex matrix effects of body fluids also contribute to separation difficulties. Thirdly, enrichment is a highly challenging task owing to low exosome concentrations. Traditional methods, such as ultracentrifugation and size-exclusion chromatography, fall short in terms of their abilities to precisely separate and analyze exosomes. On the other hand, microfluidics has emerged as a robust tool for the efficient analysis of complex biological samples and is characterized by miniaturization, precise control, high throughput, automation, and integration. Firstly, the operability, integrability, and modifiability of a microfluidics system facilitate exosome separation and purification based on surface properties, size, charge, and polarity. Secondly, the use of a microfluidics approach, with its high throughput, low reagent consumption, and multichannel manipulability, greatly facilitates preparing exosomes and enhancing their concentrations. Thirdly, microfluidics ensures that diverse separation methods are compatible with downstream analysis techniques. Exosomes are highly heterogeneous; hence, they are classified by type and subpopulation (according to origin, size, molecular markers, functions, etc.). This paper first discusses microfluidics techniques for separating exosomes and examines various separation strategies grounded in the physicochemical properties of exosomes. We then analyze exosome detection methodologies that use microfluidics platforms and encompass traditional group-exosome analysis techniques and novel single-exosome analysis approaches. Finally, we discuss future clinical applications of microfluidics technology in exosome research, particularly its potential for diagnosing and treating diseases, thereby underscoring the applications value of microfluidics technology in the realm of personalized and precision medicine. Furthermore, cutting-edge microfluidics platforms offer novel perspectives for purifying and preparing EVs owing to precise fluid control, integration, miniaturization, and high-throughput characterization. EV populations, subpopulations, and single vesicles can be purified based on their physicochemical properties and microfluidics features. Comprehensive lab-on-a-chip methods are promising in terms of separating EVs based on traits, such as size, surface markers, and charge, and for obtaining highly pure EVs. Recycled EV samples can be prepared by controlling the high-throughput and multichannel capabilities of microfluidics approaches. The transition from bulk EV analysis to single-vesicle analysis provides opportunities to explore the heterogeneous nature of EVs, thereby augmenting their potential for disease diagnosis.

For centuries, a competitive evolutionary race between prokaryotes and related phages or other mobile genetic elements has led to the diversification of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR‑associated sequence (Cas) genome‑editing systems. Among the different CRISPR/Cas systems, the CRISPR/Cas9 system has been widely studied for its precise DNA manipulation; however, due to certain limitations of direct DNA targeting, off‑target effects and delivery challenges, researchers are looking to perform transient knockdown of gene expression by targeting RNA. In this context, the more recently discovered type VI CRISPR/Cas13 system, a programmable single‑subunit RNA‑guided endonuclease system that has the capacity to target and edit any RNA sequence of interest, has emerged as a powerful platform to modulate gene expression outcomes. All the Cas13 effectors known so far possess two distinct ribonuclease activities. Pre‑CRISPR RNA processing is performed by one RNase activity, whereas the two higher eukaryotes and prokaryotes nucleotide‑binding domains provide the other RNase activity required for target RNA degradation. Recent innovative applications of the type VI CRISPR/Cas13 system in nucleic acid detection, viral interference, transcriptome engineering and RNA imaging hold great promise for disease management. This genome editing system can also be employed by the Specific High Sensitivity Enzymatic Reporter Unlocking platform to identify any tumor DNA. The discovery of this system has added a new dimension to targeting, tracking and editing circulating microRNA/RNA/DNA/cancer proteins for the management of cancer. However, there is still a lack of thorough understanding of the mechanisms underlying some of their functions. The present review summarizes the recent updates on the type VI CRISPR/Cas system in terms of its structural and mechanistic properties and some novel applications of this genome‑editing tool in cancer management. However, some issues, such as collateral degradation of bystander RNA, impose major limitations on its in vivo application. Furthermore, additional challenges and future prospects for this genome editing system are described in the present review.

Exosome acts as an outstanding biomarker for ongoing studies, diagnosis and prognosis of multiples diseases. Therefore, the call for economically and efficiently isolating a large number of exosomes is an active area of investigation. However, to date, the challenges including complex isolated procedure, uneconomical equipment, low protein content and distinct loss in the particle number of exosomes etc. still encounter in exosome isolation. Polyethylene glycol (PEG)-induced exosome isolation increasingly attracts wide attention of scientists. PEG precipitation reveals higher performance in the yield of exosomes among multiple common isolation techniques. PEG-based precipitation is a temporarily low-purity, but inexpensive, time-save, labor-less, convenient and high-yield technique to gain exosomes with high biological activities. Hence, the PEG-based exosome isolation approach wins the endorsement of experimental workers. Herein, we summary the existing knowledge on procedures of PEG-based exosomes separation from different biospecimens, the binding process of PEG to exosomes, some notices, demerits, merits of PEG-based exosome isolation, and at last the advantages by combining PEG-precipitation to other techniques for exosome isolation, with a view to eliciting profound insights for investigators who recruit PEG for exosome separation, and advancing references for the standardization of PEG-based exosome isolation in future.

Exosomes are extracellular vesicles secreted by cells and are rich in genetic material and proteins. The surfaces of exosome membranes contain many blast-specific markers that provide an important basis for disease diagnosis, progression, and treatment. Herein, we searched the Web of Science core collection (SCI-EXPENED) database for research and review articles on "exosomes" and "biomarkers" or "diagnostics" or "liquid biopsy" as research topics between 2010 and 2024. Bibliometric analysis revealed that exosomes have received increasing levels of attention as disease biomarkers, with China contributing the most to these studies. Herein, we focus on marker diagnoses for cancer, inflammation, and diabetes, as well as neurodegenerative and cardiovascular diseases. Chromatography, mass spectrometry, Raman spectroscopy, and other techniques are typically used to analyze exosomal nucleic acids, proteins, and metabolites, with commonly used test samples including plasma, serum, urine, saliva, cerebrospinal fluid, and other bodily fluids. Research into exosomes as tumor markers has mainly focused on eight highly prevalent cancers, including lung, breast, and prostate cancers. This paper focuses on exosomes as disease biomarkers and uses a bibliometric tool system to analyze the use of exosomes and their contents as biomarkers in the disease diagnosis field between 2010 and 2024, analyzes development prospects, and discusses future exosome-mediated efforts for diagnosing and treating diseases, and is expected to provide a reference for studying and applying exosomes as disease markers.

Exosomes are bilayered vesicles derived from living cells and bacteria that are loaded with abundant biomolecules, such as proteins and nucleic acids. As an important medium of remote cell communication, exosomes are closely related to the occurrence and development of a number of diseases, including those involving tumors and inflammation. The isolation and enrichment of exosomes in complex biosystems is greatly significant for the diagnosis, prognosis, and detection of diseases, as well as in molecular-mechanism research. However, exosomes are usually nanoscale size distribution and widely existed in complex biological samples, including blood, tissue fluids, and urine, which bring difficulties and challenges to the isolation and enrichment of exosomes. To address this issue, several methods based on the physical properties of exosomes have been developed. For example, exosomes can be obtained by ultracentrifugation at high centrifugal force based on density differences; they can also be isolated and enriched by size-exclusion chromatography and ultrafiltration based on size heterogeneity. Exosomes can also be separated in high yields but with low purities using commercial polymer-coprecipitation-based isolation kits. While the abovementioned methods can be used to isolate and enrich exosomes in a highly efficient manner, accurately distinguishing interfering particles, including protein aggregates and microvesicles, in biosystems is still difficult, resulting in the poor purity of exosome isolation and enrichment. Affinity ligands are widely used during the affinity isolation and enrichment of exosomes. Antibodies exhibit high selectivity and affinity; consequently exosomes can be captured highly selectively by exploiting specific antigen/antibody interactions. However, antibodies also have some limitations, including complex preparation procedures, high costs, and poor stability. Chemical affinity ligands, such as aptamers, peptides, and small molecules, are also widely used to isolate and enrich exosomes. As a kind of molecular recognition tool, peptides contain a variety of amino acids and exhibit many advantages, including good biocompatibility, low immunogenicity, and design flexibility. Solid-phase synthesis strategies have rapidly developed, thereby providing a basis for automated and large-scale peptide synthesis. Affinity peptides have been widely used to recognize and analyze target biomolecules in complex physiological environments in a highly selective manner. A series of protein-targeting peptides has been reported based on the biomolecular characteristics of exosomes. These affinity peptides can be specifically anchored onto highly enriched transmembrane proteins on exosome surfaces, thereby enabling the efficient and highly selective isolation and enrichment of exosomes in complex systems. Additionally, exosomes contain stable bilayer membranes consisting of abundant and diverse phospholipid molecules. The development of phospholipid-molecule-targeting peptides is expected to effectively eliminate interference from protein aggregates and other particles. In addition to differences in the compositions of phospholipids in biofilms, exosomes are smaller and more curved than apoptotic bodies and microvesicles. A series of affinity peptides capable of inducing and sensing high membrane curvatures are widely used to isolate and enrich exosomes. The tumor microenvironment can produce and release tumor-derived exosomes that are buried in a large number of normal cell-derived exosomes. Accordingly, pH-responsive peptides have been designed and modified based on the acidic environments of tumor-derived exosomes, which were accurately and tightly anchored via peptide insertion and folding. Focusing on the current status of exosome research, this paper introduces and summarizes current and widely used methods for isolating and enriching exosomes. Various exosome-targeting peptide-design and screening principles are introduced based on the characteristics and advantages of peptides. The applications of these peptides to the isolation and enrichment of exosomes are also summarized, thereby providing strong guidance for the efficient and highly selective isolation and enrichment of exosomes in complex life-related systems.

Wound healing is a natural, however complex, tissue repair and regeneration mechanism. Understanding the cascade of biological events associated with wound healing facilitates scientists in designing topical skin formulations with enhanced therapeutic outcomes. In recent years, several innovative approaches have been utilized to treat wounds. Hyaluronic acid (HA)-based formulations have shown promising results. The current manuscript provides a systematic review of various aspects of HA, including its structure, synthesis, mechanism involved in wound healing, and various formulations developed using HA to treat wounds. Covered are innovative treatment strategies explicitly emphasizing nanocarrier-based approaches. Various patents wherein HA has been used to treat wounds are also summarized with the help of a Google patent search. Diving deep, clinical perspectives, toxicity aspects, and application of computational chemistry in HA research are also discussed.

Extracellular vesicles (EVs), isolated through techniques such as liquid biopsy, have emerged as crucial biomarkers in various diseases, including cancer. EVs were dismissed initially as cellular debris, EVs are now recognized for their role in intercellular communication, carrying proteins, RNAs, and other molecules between cells. Their stability in biofluids and ability to mirror their parent cells' molecular composition make them attractive candidates for non-invasive diagnostics. EVs, including microvesicles and exosomes, contribute to immune modulation and cancer progression, presenting both therapeutic challenges and opportunities. However, despite advances in analytical techniques like high-resolution microscopy and nanoparticle tracking analysis (NTA), standardization in EV isolation and characterization remains a hurdle. Cutting-edge technologies, such as atomic force microscopy and Raman tweezers microspectroscopy, have enhanced our understanding of single EVs, yet issues like low throughput and high technical complexity limit their widespread application. Other technologies like transmission electron microscopy, cryogenic transmission electron microscopy, super-resolution microscopy, direct stochastic optical reconstruction microscopy, single-molecule localization microscopy, tunable resistive pulse sensing, single-particle interferometric reflectance imaging sensor, flow cytometry, droplet digital analysis, total internal reflection fluorescence also contribute to EV analysis. Future research must focus on improving detection methods, developing novel analytical platforms, and integrating artificial intelligence to enhance the specificity of EV characterization. The future of EV research holds promise for breakthroughs in precision medicine, with a collaborative effort needed to translate these advancements into clinical practice.

Melanoma, an aggressive form of skin cancer, presents significant therapeutic challenges due to its resistance to conventional treatments and propensity for metastasis. Exosomes, nanoscale vesicles secreted by a wide variety of cells, have emerged as promising tools for developing novel melanoma therapies. Exosome-based therapeutic approaches offer several advantages, including inherent biocompatibility, low immunogenicity, and the ability to cross biological barriers. This review explores the therapeutic potential of exosomes in melanoma treatment, focusing on their multifaceted roles in modulating tumor cell behavior, enhancing anti-tumor immune responses, and serving as targeted drug delivery vehicles. We discuss various strategies employed to engineer exosomes for enhanced therapeutic efficacy, including loading them with chemotherapeutic agents, small interfering RNAs (siRNAs), microRNAs (miRNAs), and immunomodulatory molecules. Additionally, we highlight the potential of exosomes derived from diverse sources to enhance anti-cancer effects. Furthermore, we address the challenges and future directions in translating exosome-based therapies from bench to bedside, emphasizing the need for standardized isolation and manufacturing protocols, as well as rigorous preclinical and clinical evaluations to unlock the full therapeutic potential of exosomes in the fight against melanoma.

Tendinopathy is a common musculoskeletal disorder in which a significant number of patients do not attain effective therapeutic outcomes. The extent of the inflammatory response and the dynamics of collagen synthesis metabolism are critical factors that influence the intrinsic self-repair capacity of tendons. However, the poor microenvironment within the tendon significantly impedes the self-repair process in tendinopathy. In this study, an injectable tendon-derived decellularized extracellular matrix (tdECM) hydrogel was utilized to treat tendinopathy. This hydrogel provides a more cytocompatible microenvironment while retaining certain bioactive factors of native tendon extracellular matrix (ECM), compared to collagen hydrogel. Notably, it was discovered for the first time that the tdECM hydrogel promotes M2 macrophage polarization, thereby exerting an anti-inflammatory effect in vivo. Furthermore, utilizing tdECM as a carrier for the sustained release of tendon-derived stem cells exosomes (TDSCs-Exos), our findings from both in vitro and in vivo studies indicate that the tdECM hydrogel, in conjunction with exosomes, demonstrated a pronounced synergistic enhancement in modulating inflammation, promoting M2 macrophage polarization, and facilitating tendon regeneration and repair efficacy. These results suggest its potential as a promising therapeutic strategy for tendon disorders.

Ischemic stroke is the major type of stroke and one of the main causes of morbidity, mortality, and long-term disability worldwide. Microglia play a complex and crucial role in stroke. They are the primary immune cells in the brain and can rapidly respond to the pathological changes caused by stroke. They promote neuroprotection and repair after ischemic stroke through various mechanisms, such as activation and polarization, dynamic interactions with other cells (neurons, astrocytes, oligodendrocytes, vascular endothelial cells, etc.), and phagocytosis to clear dead cell debris. Among the multiple pathways through which microglia exert their neuroprotective effects, the secretion of extracellular vesicles is one of the most important. The focus of this review is to analyze the latest progress in research on ischemic stroke related to microglia-derived extracellular vesicles, discuss their mechanisms of action, and provide new strategies for improving stroke prognosis. To obtain relevant articles, we conducted a comprehensive search in Pubmed and Web of Science, with keywords related to ischemic stroke and microglia-derived extracellular vesicles or exosomes. A total of 59 articles were included in the review. Existing studies have shown that after a stroke occurs, microglia release extracellular vesicles containing proteins, nucleic acids, metabolites, etc. These vesicles target corresponding receptor cells and can slow down the development of stroke and improve stroke outcomes through various means, such as reducing neuronal apoptosis, inhibiting neuronal autophagy, suppressing neuronal ferroptosis, preventing neuronal pyroptosis, alleviating inflammatory responses, reducing glial scar formation, promoting myelin regeneration and repair, and facilitating blood-brain barrier repair.

Exosomes are extracellular vesicles ranging from 40 to 100 nm in diameter that mediate intercellular communication by transferring proteins, lipids, nucleic acids, and other metabolites. In the context of cancer, exosomes influence the tumor microenvironment by carrying regulatory RNAs such as miRNA, circRNA, and lncRNA. They originate from various cells, including adipocytes, fibroblasts, and hepatocellular carcinoma (HCC) cells, and can either promote or inhibit cancer progression through pathways like MAPK and PI3K-Akt.

This review aims to explore the role of exosomes in the progression of solid cancers, emphasizing their self-induced activation mechanisms and how they modulate tumor behavior.

A comprehensive review of recent literature was conducted, focusing on studies that investigated the biological functions of exosomes in solid tumor progression, including their molecular cargo, cellular origin, and involvement in signaling pathways.

Findings from multiple studies indicate that cancer-derived exosomes contribute to tumor proliferation, metastasis, and therapy resistance by enhancing communication within the tumor microenvironment. These vesicles activate oncogenic pathways and can serve as biomarkers or therapeutic targets due to their role in disease modulation.

Exosomes play a pivotal role in solid cancer progression and offer significant potential in advancing our understanding of tumor biology. Their capacity to influence key signaling pathways and facilitate intercellular communication makes them promising candidates for novel diagnostic and therapeutic strategies.

Exosomes, as vital mediators of intercellular communication, play a critical role in the progression of cardiovascular disease (CVD). Recently, macrophage-derived exosomes (Mφ-Exos) have garnered increasing attention because of their significant potential in early diagnosis, pathological processes, and therapeutic applications for CVD. Exosomes contain diverse nucleic acids (e.g., miRNAs, mRNAs, and long noncoding RNAs (lncRNAs)) and proteins, which serve as specific biomarkers that regulate various stages of CVD. For example, miRNAs encapsulated within exosomes (e.g., miR-21, miR-133a, and miR-155) are closely associated with atherosclerosis, myocardial infarction, coronary artery disease, and stroke, and changes in their abundance can serve as diagnostic and prognostic indicators. Additionally, the composition of Mφ-Exos, including miRNAs, lipids, and proteins, plays a significant role in the initiation, progression, and inflammation of CVD. Research on Mφ-Exos provides new directions for early diagnosis, mechanistic exploration, and novel therapeutic targets in CVD. However, challenges remain regarding exosome isolation and identification technologies. Future studies need to further explore the biological properties of exosomes and develop more efficient, economical, and straightforward isolation methods. This review summarizes the multifaceted regulatory roles of Mφ-Exos in CVD, encompassing key processes such as inflammation, angiogenesis, metabolism, and cell death. Research has shown that M1-Exos promote the progression and exacerbation of CVD through pro-inflammatory and pro-fibrotic mechanisms, while M2-Exos demonstrate significant therapeutic potential via anti-inflammatory, pro-angiogenic, and metabolic reprogramming pathways. These findings not only reveal the complex mechanisms of Mφ-Exos in CVD but also provide new perspectives and potential targets for early diagnosis and precision treatment of the disease.

The targeted delivery of therapeutics to internal organs to, for example, promote healing or apoptosis holds promise in the treatment of numerous diseases1-4. Currently, the prevailing delivery modality relies on the circulation; however, this modality has substantial efficiency, safety and/or controllability limitations5-9. Here we report a battery-free, chipless, soft nanofluidic intracellular delivery (NanoFLUID) patch that provides enhanced and customized delivery of payloads in targeted internal organs. The chipless architecture and the flexible nature of thin functional layers facilitate integration with internal organs. The nanopore-microchannel-microelectrode structure enables safe, efficient and precise electroperforation of the cell membrane, which in turn accelerates intracellular payload transport by approximately 105 times compared with conventional diffusion methods while operating under relatively low-amplitude pulses (20 V). Through evaluations of the NanoFLUID patch in multiple in vivo scenarios, including treatment of breast tumours and acute injury in the liver and modelling tumour development, we validated its efficiency, safety and controllability for organ-targeted delivery. NanoFLUID-mediated in vivo transfection of a gene library also enabled efficient screening of essential drivers of breast cancer metastasis in the lung and liver. Through this approach, DUS2 was identified as a lung-specific metastasis driver. Thus, NanoFLUID represents an innovative bioelectronic platform for the targeted delivery of payloads to internal organs to treat various diseases and to uncover new insights in biology.

Beyond their well-established adhesive properties, polydopamine (pDA) and pDA-like materials are emerging as superior alternatives to conventional optical indicators in biosensing applications due to their exceptional biocompatibility, tunable optical properties, and high sensitivity, arising from their eumelanin-like physicochemical characteristics. These materials attract significant attention for their ability to function as optical probes and transducers, enabling precise and sensitive detection in complex biological environments. This review highlights recent advancements in developing pDA-based optical probes, emphasizing strategies for fine-tuning synthetic parameters to optimize material properties, clarifying the fundamental sensing mechanisms underlying pDA-based systems, and exploring their potential roles in addressing global healthcare challenges. By facilitating early disease detection, real-time monitoring, and targeted therapeutic intervention, pDA-based optical probes offer transformative solutions to pressing biomedical needs. Through a comprehensive examination of cutting-edge research, this review aims to illuminate how the unique attributes of pDA materials drive innovation in biosensing technologies and contribute to improved healthcare outcomes.

The serum prostate-specific antigen (PSA) testing is widely used for prostate cancer (PCa) screening but suffers from poor specificity, leading to unnecessary biopsies and overtreatment. The significant potential of extracellular vesicles (EVs) in cancer diagnosis has driven the development of efficient methods to isolate and identify EV biomarkers from large-scale clinical samples. Here, we systematically evaluate five commonly used EV isolation techniques through proteomic profiling of plasma-derived EVs, endorsing TiO2-based chemical affinity capture as a superior approach for analyzing EVs from complex clinical samples. This method demonstrates exceptional advantages in speed, throughput, reproducibility, and protein coverage. Using this optimized workflow, we analyzed plasma EVs from 80 patients with PCa and benign prostatic hyperplasia (BPH), identifying growth differentiation factor 15 (GDF15) as a compelling biomarker with a predictive power (AUC) of 0.908 for PCa. Extensive validation across independent cohorts comprising 457 samples, including plasma EVs and prostate tissues, confirmed GDF15's ability to distinguish PCa from BPH and stratify PCa stages. Notably, the combination of GDF15 with PSA further enhanced diagnostic efficiency, particularly for patients in the PSA diagnostic gray zone. This study establishes a robust workflow for EV protein analysis in large clinical cohorts and highlights EV-GDF15 as a promising biomarker for noninvasive PCa diagnosis.