Disposable plasmonic metasurfaces with high biosensing performance are urgently sought for clinical label-free detection. Low-cost aluminum (Al) and titanium nitride (TiN) offer promising alternatives to noble metals for constructing these metasurfaces. However, Al suffers from limited chemical stability, and TiN exhibits weak plasmonic effects, both of which hinder their application in meta-biosensing. Here we integrate their complementary advantages and propose the TiN/Al meta-biosensors. They not only empower the unique near-field enhancement for sensing by TiN/Al hybrid plasmonic modes, but also construct a robust TiN armor against external wear, heat, moisture and corrosion during the bio-detection process. Compared to traditional gold-based counterparts, our meta-biosensors offer superior optical sensitivity at a much lower cost and with fewer pretreatment steps. The excellent biosensing performance facilitates the development of a high-throughput detection system for serum small extracellular vesicles (sEVs), aiding in the diagnosis and follow-up of prostate cancer. The sEVs meta-biosensing demonstrates a diagnostic sensitivity of 100% for significantly distinguishing early cancer, breaking through the conventional testing limitation. Moreover, it doubles the prediction accuracy of cancer recurrence risk following surgery. Our research highlights the potential for large-scale development of powerful meta-biosensors based on non-noble materials, opening up significant opportunities in cancer diagnosis and prognosis.

In recent years, the significant role of anticancer drugs in cancer treatment has garnered considerable attention. However, the application of these drugs is largely limited by their short half-life in blood circulation, low cellular uptake efficiency, and off-target effects. Exosomes, which serve as crucial messengers in intercellular communication, exhibit unique advantages in molecular delivery compared to traditional synthetic carriers, thereby offering new possibilities for modern drug delivery systems. Exosomes possess organotropic functions and are naturally produced by cells, making them promising candidates for natural drug delivery systems with organotropic properties and minimal side effects. These naturally derived carriers can achieve stable, efficient, and selective delivery of anticancer drugs, thereby enhancing the efficacy and potential of anticancer agents in cancer immunotherapy. This review provides a concise overview of the unique characteristics of exosomes related to anticancer drug delivery, strategies for utilizing exosomes as carriers in cancer therapy, and the latest advancements in the field.

Exosomes are microscopic vesicles released by cells that transport various biological materials and play a vital role in intercellular communication. When they are engineered, they serve as efficient delivery systems for therapeutic agents, making it possible to precisely deliver active pharmaceutical ingredients to organs, tissues, and cells. Exosomes' pharmacokinetics, or how they are transported and metabolized inside the body, is affected by several factors, including their source of origination and the proteins in their cell membranes. The pharmacokinetics and mobility of both native and modified exosomes are being observed in living organisms using advanced imaging modalities such as in vitro-in vivo simulation, magnetic resonance imaging, and positron emission tomography. Establishing comprehensive criteria for the investigation of exosomal pharmacokinetic is essential, given its increasing significance in both therapy and diagnostics. To obtain a thorough understanding of exosome intake, distribution, metabolism, and excretion, molecular imaging methods are crucial. The development of industrial processes and therapeutic applications depends on the precise measurement of exosome concentration in biological samples. To ensure a seamless incorporation of exosomes into clinical practice, as their role in therapeutics grows, it is imperative to conduct a complete assessment of their pharmacokinetics. This review provides a brief on how exosome-based research is evolving and the need for pharmacokinetic consideration to realize the full potential of these promising new therapeutic approaches.

Photothermal and photodynamic therapies represent effective modalities for combatting bacteria and tumor cells. However, therapeutic outcomes are constrained by limitations related to the heat and reactive oxygen species (ROS) transfer distance from photosensitizers to targets. To address this issue, we have devised and developed exosome-decorated bio-heterojunctions (E-bioHJ) consisted of MXene (Ti3C2), liquid metal (LM) and exosomes sourced from CT26 cells to enhance the phototherapeutic consequences. Engineering E-bioHJ enhances phototherapeutic effect in antibacterial and anti-tumor treatment, which is ascribed to reducing transfer distance of the heat and ROS. When adorned with exosomes, E-bioHJ is targetedly delivered into the cytoplasm of tumor cells to generate amount heat and ROS under 808 nm near-infrared radiation, which further induces mitochondrial dysfunction and apoptosis/necroptosis. As envisaged, this study presents a novel tactic to enhance the antibacterial and anti-tumor efficacy of biomaterials through reducing the heat and ROS delivery travel distance.

The pervasive global health concern of breast cancer necessitates the development of innovative therapeutic interventions to enhance efficacy and mitigate adverse effects. Chitosan and hyaluronic acid, recognized for their biocompatibility and biodegradability, present compelling options for the novel drug delivery systems and therapeutic platforms in the context of breast cancer management. This review will delineate the distinctive attributes of chitosan and hyaluronic acid, encompassing their inherent anticancer properties, targeting capabilities, and suitability for chemical modifications along with nanoparticle development. These characteristics render them exceptionally well-suited for the fabrication of nanoparticles and hydrogels. The intrinsic anticancer potential of chitosan, in conjunction with its mucoadhesive properties, and the robust binding affinity of hyaluronic acid to CD44 receptors, facilitate specific drug delivery to the malignant cells, thus circumventing the limitations inherent in traditional treatment modalities such as chemotherapy. The incorporation of these materials into nanocarriers allows for the co-delivery of therapeutic agents, thereby potentiating synergistic effects, while hydrogel systems provide localized, controlled drug release and facilitate tissue regeneration. An analysis of advancements in their synthesis, functionalization, and application is presented, while also acknowledging challenges pertaining to scalability and clinical translation.

Premature ovarian insufficiency (POI) refers to the severe decline or failure of ovarian function in women younger than 40 years of age. It is a serious hazard to women's physical and mental health, but current treatment options are limited. Mesenchymal stem cell-derived exosomes (MSC-Exo) exhibit promising potential as a therapeutic approach for POI. However, their clinical application is hindered by their instability and low long-term retention rate in vivo.

In this study, miR-21 was identified as the predominant miRNA with low-expression in follicular fluid exosomes of POI patients and was shown to possess antiapoptotic activity. Next, we loaded miR-21 agomir to MSC-Exo to form Agomir21-Exo, which significantly reversed the apoptosis of granulosa cells in vitro. Moreover, we successfully developed GelMA hydrogel microspheres for encapsulating Agomir21-Exo through microfluidic technology, named GelMA-Ag21Exo, which had good injectability and significantly enhanced the stability and long-term retention of Agomir21-Exo in mice through sustained release. The release of Agomir21-Exo from GelMA-Ag21Exo notably alleviated the apoptosis of ovarian granulosa cells and improved the ovarian reserve and fertility in POI mice.

Our findings illustrate that activating miR-21 through Agomir21-Exo could improve the function of ovarian granulosa cells. The GelMA-Ag21Exo enhanced the exosome-based therapeutic efficacy of the Agomir21-Exo in vivo. These findings provide a novel and promising treatment strategy for POI patients.

Graft-versus-host disease (GvHD) is a prevalent complication following allogeneic hematopoietic stem cell transplantation (HSCT) and is characterized by relatively high morbidity and mortality rates. GvHD can result in extensive systemic damage in patients following allogeneic HSCT (allo-HSCT), with the skin, gastrointestinal tract, and liver frequently being the primary target organs affected. The severe manifestations of acute intestinal GvHD often indicate a poor prognosis for patients after allo-HSCT. Endoscopy and histopathological evaluation remain employed to diagnose GvHD, and auxiliary examinations exclude differential diagnoses. Currently, reliable serum biomarkers for the diagnosis and differential diagnosis of GvHD are scarce. As an essential part of standard transplant protocols, early application of immunosuppressive drugs effectively prevents GvHD. Among them, steroids represent first-line therapeutic agents, and the JAK2 inhibitor ruxolitinib represents the second-line therapeutic agent. Currently, no efficacious treatment modality exists for steroid-resistant aGvHD. Therefore, the diagnosis and treatment of GvHD still face significant medical demands. Extracellular vesicles (EVs) are nanometer to micrometer-scale biomembrane vesicles containing various bioactive components, such as proteins, nucleotides, and metabolites. Distinctive changes in serum-derived EV components occur in patients after allo-HSCT; Hence, EVs are expected to be potential biomarkers for diagnosing and treating GvHD. Furthermore, cell-free therapeutics characterized by EVs derived from mesenchymal stem cells (MSCs) have manifested remarkable therapeutic efficacy in preclinical models and preclinical trials of GvHD. Customized engineered EVs with fewer toxic and side effects for the combined treatment of GvHD hold broad prospects for clinical translation. This review article examines the potential value of translating EVs into clinical applications for the diagnosis and treatment of GvHD. It summarizes the latest advancements and prospects of engineered EVs applying GvHD.

Extracellular vesicles (EVs) are emerging as critical mediators of intercellular communication in the tumor microenvironment (TME), profoundly influencing cancer progression. These nano-sized vesicles, released by both tumor and stromal cells, carry a diverse cargo of proteins, nucleic acids, and lipids, reflecting the dynamic cellular landscape and mediating intricate interactions between cells. This review provides a comprehensive overview of the biogenesis, composition, and functional roles of EVs in cancer, highlighting their significance in both basic research and clinical applications. We discuss how cancer cells manipulate EV biogenesis pathways to produce vesicles enriched with pro-tumorigenic molecules, explore the specific contributions of EVs to key hallmarks of cancer, such as angiogenesis, metastasis, and immune evasion, emphasizing their role in shaping TME and driving therapeutic resistance. Concurrently, we submit recent knowledge on how the cargo of EVs can serve as a valuable source of biomarkers for minimally invasive liquid biopsies, and its therapeutic potential, particularly as targeted drug delivery vehicles and immunomodulatory agents, showcasing their promise for enhancing the efficacy and safety of cancer treatments. By deciphering the intricate messages carried by EVs, we can gain a deeper understanding of cancer biology and develop more effective strategies for early detection, targeted therapy, and immunotherapy, paving the way for a new era of personalized and precise cancer medicine with the potential to significantly improve patient outcomes.

Natural killer cell-derived exosomes (NK-Exos) hold great promise as immune modulators and immunotherapeutics against cancer due to their intrinsically latent anti-tumor effects. They use these nanosized vesicles to deliver cytotoxic molecules, such as perforin, granzymes, and miRNAs, directly to cancer cells to kill them, avoiding immune suppression. NK-Exos has particular efficacy for treating aggressive breast cancer by modulating the TME to activate the immune response and suppress immunosuppressive factors. Bioengineering advances have extended the therapeutic potential of NK-Exos, which permits precise tumor cell targeting and efficient delivery of therapeutic payloads, including small RNAs and chemotherapeutic agents. In engineered NK-Exos, sensitization of cancer cells to apoptosis, reduction of tumor growth, and resistance to drugs have been demonstrated to be highly effective. When combined, NK-Exos synergizes with radiotherapy, chemotherapy, or checkpoint inhibitors, enhancing therapeutic efficacy, and minimizing systemic toxicity. This review emphasizes the critical role of NK-Exos in breast cancer treatment, their integration into combination therapies, and the need for further research to overcome existing limitations and fully realize their clinical potential.

Small extracellular vesicles (sEVs) are a promising vehicle for drug delivery because of their good biocompatibility and nontoxicity. The drug loading and encapsulation efficiencies of them are not satisfactory. This is especially the case when drugs are loaded by co-incubation. In this situation, as the difference in drug concentration between the inside and outside of the membrane of ordinary sEVs decreases, the drugs cannot diffuse efficiently into the inside of the vesicles. As a result, the drug loading efficiency is low. In this study, engineered yeast-derived small extracellular vesicles derived from Pichia pastoris X33 (XPP-sEVs) engineered with carboxylesterase 1 (CES1) were constructed using the "esterase-responsive active loading" method, which is based on the concept of prodrug design and guided by the strategy of immobilized enzymes, to improve the loading efficiency of methyl salicylate (MS) to about twice as much. This was achieved by engineering the CES1-contained small extracellular vesicles to catalyze the esterase hydrolysis reaction of MS to establish a continuous MS transmembrane concentration gradient for efficient loading of the active drugs, including methyl salicylate and its hydrolyzed active product salicylic acid. The results showed that the enzyme activity of the CES1-sEVs group finally reached 7.88 ± 0.43 U/mL, and the drug loading efficiency was about doubled. The results of drug release from the engineered extracellular vesicles showed that the release of the drug reached equilibrium around 100 min-2 h, during which there was no sudden release of the MS, and the final amount of the drug released could be increased by 12.34 % compared with the emulsion dosage form of the MS. Overall, the CES1-sEVs prepared in this study significantly improved the drug-loading efficiency of MS without affecting the anti-inflammatory activity of MS. The MS-CES1-sEVs prepared in this study are non-toxic and have a bright application prospect in the treatment of skin inflammation.

As we progress into the 21st century, cancer stands as one of the most dreaded diseases. With approximately one in every four individuals facing a lifetime risk of developing cancer, cancer remains one of the most serious health challenges worldwide. Its multifaceted nature makes it an arduous and tricky problem to diagnose and treat. Over the years, researchers have explored plenty of approaches and avenues to improve cancer management. One notable strategy includes the study of extracellular vesicles (EVs) as potential biomarkers and therapeutics. Among these EVs, exosomes have emerged as particularly promising candidates due to their unique characteristic properties and functions. They are small membrane-bound vesicles secreted by cells carrying a cargo of biomolecules such as proteins, nucleic acids, and lipids. These vesicles play crucial roles in intercellular communication, facilitating the transfer of biological information between cell-to-cell communication. Exosomes transport cargoes such as DNA, RNA, proteins, and lipids involved in cellular reprogramming and promoting cancer. In this review, we explore the molecular composition of exosomes, significance of exosomes chemistry in cancer development, and its theranostic application as well as exosomes research complications and solutions.

Drug-induced liver injury (DILI) involves multifaceted pathogenesis, necessitating effective therapeutic strategies. Wnt2, secreted by liver sinusoidal endothelial cell (LSEC), activates the Wnt/β-catenin signaling pathway to promote hepatocyte proliferation after injury. To address the dual challenges of targeted delivery and phagocytosis evasion, we develop a combined "eat me/don't eat me" strategy. RLTRKRGLK (RLTR) peptide-functionalized exosomes are engineered by inserting DMPE-PEG2000-CRLTRKRGLK into the lipid membrane of exosome derived from bEnd.3 cell. Surface-displayed RLTR mediates exosomal enrichment in LSEC, while CD47 engineering reduces macrophage clearance via "don't eat me" signaling. Then, lentiviral transfection enables stable encapsulation of functional Wnt2 mRNA into ExoCD47 (designated Wnt2@ExoCD47). In both acetaminophen (APAP) and dimethylnitrosamine (DMN)-induced murine liver injury models, RLTR-Wnt2@ExoCD47 demonstrates LSEC-specific targeting and significant hepatoprotection. This engineered exosome platform provides a therapeutic strategy for DILI.

Post-surgical tumor recurrence poses a major challenge in cancer treatment due to residual tumor cells and surgery-induced immunosuppression. Here, we developed hybrid nanoparticles, termed T-DCNPs, designed to promote antigen-specific activation of cytotoxic CD8+ T cells while concurrently inhibiting immunosuppressive pathways within the tumor microenvironment. T-DCNPs were formulated by co-extruding lipid nanoparticles containing a transforming growth factor β inhibitor with dendritic cells that were pre-treated with autologous neoantigens derived from surgically excised tumors. By using whole tumor antigens rather than specific peptides, T-DCNPs effectively overcame tumor heterogeneity and elicited a robust, targeted immune response. In vitro studies showed that T-DCNPs enhanced CD8+ T cell proliferation and reduced programmed death-1 (PD-1) expression, leading to increased antitumor cytotoxicity. In vivo experiments, involving intratumoral injections of T-DCNPs in distant tumor and post-surgical melanoma models, demonstrated a significant reduction in distant tumor growth, decreased recurrence rates, and extended survival compared to control groups. Flow cytometry and immunohistochemistry analyses further confirmed the enhanced infiltration of activated CD8+ T cells and a marked reduction in immunosuppressive markers, including PD-1 and Foxp3, within the treated tumors. These results suggest that T-DCNPs, through the dual mechanisms of tumor antigen-specific T cell activation and immune modulation, offer a promising strategy to prevent tumor recurrence following surgery and could potentially improve the efficacy of postoperative cancer immunotherapy.

Exosomes have emerged as pivotal players in precision oncology, offering innovative solutions to longstanding challenges such as metastasis, therapeutic resistance, and immune evasion. These nanoscale extracellular vesicles facilitate intercellular communication by transferring bioactive molecules that mirror the biological state of their parent cells, positioning them as transformative tools for cancer diagnostics and therapeutics. Recent advancements in exosome engineering, artificial intelligence (AI)-driven analytics, and isolation technologies are breaking barriers in scalability, reproducibility, and clinical application. Bioengineered exosomes are being leveraged for CRISPR-Cas9 delivery, while AI models are enhancing biomarker discovery and liquid biopsy accuracy. Despite these advancements, key obstacles such as heterogeneity in exosome populations and the lack of standardized isolation protocols persist. This review synthesizes pioneering research on exosome biology, molecular engineering, and clinical translation, emphasizing their dual roles as both mediators of tumor progression and tools for intervention. It also explores emerging areas, including microbiome-exosome interactions and the integration of machine learning in exosome-based precision medicine. By bridging innovation with translational strategies, this work charts a forward-looking path for integrating exosomes into next-generation cancer care, setting it apart as a comprehensive guide to overcoming clinical and technological hurdles in this rapidly evolving field.

Cancer remains one of the most devastating diseases, severely affecting public health and contributing to economic instability. Researchers worldwide are dedicated to developing effective therapeutics to target cancer cells. One promising strategy involves inducing cellular senescence, a complex state in which cells exit the cell cycle. Senescence has profound effects on both physiological and pathological processes, influencing cellular systems through secreted factors that affect surrounding and distant cells. Among these factors are exosomes, small extracellular vesicles that play crucial roles in cellular communication, development, and defense, and can contribute to pathological conditions. Recently, there has been increasing interest in engineering exosomes as precise drug delivery vehicles, capable of targeting specific cells or intracellular components. Studies have emphasized the significant role of exosomes from senescent cells in cancer progression and therapy. Notably, chemotherapeutic agents can alter the tumor microenvironment, induce senescence, and trigger immune responses through exosome-mediated cargo transfer. This review explores the intricate relationship between cellular senescence, exosomes, and cancer, examining how different therapeutics can eliminate cancer cells or promote drug resistance. It also investigates the molecular mechanisms and signaling pathways driving these processes, highlighting current challenges and proposing future perspectives to uncover new therapeutic strategies for cancer treatment.

Virtually all cell types are capable of secreting small extracellular vesicles (sEV), which can be internalized by recipient cells, thereby serving as vehicles for intercellular communication. The cargoes of these vesicles, such as microRNAs, circular RNAs, proteins, and lipids, play significant roles in both normal cellular functions and the pathogenesis of various diseases. Diabetic Nephropathy (DN), a complication arising from diabetes, is expected to contribute to a 54% increase in the global diabetic population between 2015 and 2030, leading to substantial economic burdens on individuals and healthcare systems. sEVs, as promising biomarkers, demonstrate diverse mechanistic responses in different types of Diabetic Kidney Disease (DKD). They also hold advantages in the early prediction of renal damage. This article reviews the functional mechanisms of sEVs in DKD and their potential as therapeutic targets and biomarkers.

The intricate relationship between cancer, circadian rhythms, and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis and cancer progression. Aging is a well-established primary risk factor for cancer, while disruptions in circadian rhythms are intricately associated with the tumorigenesis and progression of various tumors. Moreover, aging itself disrupts circadian rhythms, leading to physiological changes that may accelerate cancer development. Despite these connections, the specific interplay between these processes and their collective impact on cancer remains inadequately explored in the literature. In this review, we systematically explore the physiological mechanisms of circadian rhythms and their influence on cancer development. We discuss how core circadian genes impact tumor risk and prognosis, highlighting the shared hallmarks of cancer and aging such as genomic instability, cellular senescence, and chronic inflammation. Furthermore, we examine the interplay between circadian rhythms and aging, focusing on how this crosstalk contributes to tumorigenesis, tumor proliferation, and apoptosis, as well as the impact on cellular metabolism and genomic stability. By elucidating the common pathways linking aging, circadian rhythms, and cancer, this review provides new insights into the pathophysiology of cancer and identifies potential therapeutic strategies. We propose that targeting the circadian regulation of cancer hallmarks could pave the way for novel treatments, including chronotherapy and antiaging interventions, which may offer important benefits in the clinical management of cancer.

High-grade gliomas (HGGs), including glioblastoma (GBM) in adults and diffuse intrinsic pontine glioma (DIPG) in children, are among the most aggressive and deadly brain tumors. A key factor in their resilience is the presence of glioma stem cells (GSCs), which drive tumor initiation, progression, and resistance to treatment. Targeting and eradicating GSCs holds potential for curing both GBM and DIPG. Natural killer (NK) cells, as part of the innate immune system, naturally recognize and destroy malignant cells. Recent advances in NK cell-based therapies, such as chimeric antigen receptor (CAR)-NK cells, NK cell engagers, and NK cell-derived exosomes, offer promising approaches for treating GBM and DIPG, particularly by addressing the persistence of GSCs. This review highlights these advancements, explores challenges such as the blood-brain barrier and the immunosuppressive tumor microenvironment, and proposes future directions for improving and clinically advancing these NK cell-based therapies for HGGs.

The efficacy of Bone Marrow Mesenchymal Stem Cell-derived Exosomes (BMSCs-Exo) in addressing the complexities of Polycystic Ovary Syndrome (PCOS) has been explored in a controlled experimental study using a DHEA-induced PCOS model in 6-8-week-old female NMRI mice. This research undertook an in vivo approach with fifteen female murine subjects to investigate the potential of BMSCs-Exo in promoting vascular regeneration and alleviating the adverse effects associated with PCOS. Through a strategic intervention, the study aimed to modulate the pathophysiological markers of oxidative stress and inflammation that are hallmark features of PCOS. Remarkably, the administration of BMSCs-Exo led to decreased CD31 expression in ovarian tissues, suggesting reduced angiogenesis and endothelial activation. Moreover, a significant reduction in pro-inflammatory cytokines and oxidative stress markers was noted, aligning closely with the metrics observed in the control group. These findings illuminate a promising therapeutic avenue utilizing BMSCs-Exo to recalibrate angiogenic, inflammatory, and oxidative stress responses in PCOS. This research not only contributes to the current understanding of PCOS management but also opens new doors for innovative clinical treatments.

Liver ischemia and reperfusion (I/R) injury is a reactive oxygen species (ROS)-related disease that occurs during liver transplantation and resection and hinders postoperative liver function recovery. Current approaches to alleviate liver I/R injury have limited effectiveness due to the short circulation time, poor solubility, and severe side effects of conventional antioxidants and anti-inflammatory drugs. Herein, a universal strategy is proposed to fabricate a Trojan horse-like biohybrid nanozyme (THBN) with hepatic-targeting capabilities. Tannic acid (TA) mediates adeno-associated virus (AAV8) decoration onto 2D Ti3C2 nanosheets, resulting in THBN with a size of 116.2 ± 9.5 nm. Remarkably, THBN exhibits catalase (CAT)-like activity, broad-spectrum ROS scavenging activity and targeted delivery to liver tissue owing to the presence of AAV8. Both in vivo and in vitro experiments confirmed the efficacy of THBN in attenuating liver I/R injury by mitigating inflammation and oxidative stress and inhibiting hepatocellular apoptosis. RNA-seq analysis suggests that THBN may alleviate liver I/R injury by activating the PKC pathway. The effective targeting and therapeutic capabilities of THBN represent an advancement in nanotherapeutics for hepatic ischemia‒reperfusion injury, shedding light on the promising potential of this next-generation nanotherapeutic approach.

Exosomes can be modified and designed for various therapeutic goals because of their unique physical and chemical characteristics. Researchers have identified tumor-derived exosomes (TEXs) as significant players in cancer by influencing tumor growth, immune response evasion, angiogeneis, and drug resistance. TEXs promote the production of specific proteins important for cancer progression. Due to their easy accessibility, TEXs are being modified through genetic, drug delivery, membrane, immune system, and chemical alterations to be repurposed as vehicles for delivering drugs to improve cancer treatment outcomes. In the complex in vivo environment, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) system encounters challenges from degradation, neutralization, and immune responses, emphasizing the need for strategic distribution strategies for effective genome editing. Engineered exosomes present a promising avenue for delivering CRISPR/Cas9 in vivo. In this review, we will explore different techniques for enhancing TEXs using various engineering strategies. Additionally, we will discuss how these exosomes can be incorporated into advanced genetic engineering systems like CRISPR/Cas9 for possible therapeutic uses.

The incidence and mortality rate of liver cancer are on the rise worldwide and effective therapeutic strategies are needed. Previous studies demonstrated that exosomes and exosome-like nanoparticles (ELNs) have numerous biological activities including antioxidant, anti-tumor, and anti-inflammatory effects. In this study, ELNs were successfully isolated for the first time from Radix Polygoni Multiflori (RPM) juice by ultracentrifugation. This indicated that RPM-ELNs could be internalized by hepatoma cells effectively and inhibit their proliferation and migration in vitro. RNA sequencing and qPCR experiments were performed, and the results of bioinformatic analyses revealed that RPM-ELNs could globally regulate expression levels of numerous genes associated with cancer and the cell cycle. In addition, it showed that RPM-ELNs mainly target liver tissue of mice in vivo.

Natural killer (NK) cell-derived exosomes (NK-Exos) are emerging as a promising avenue in cancer immunotherapy due to their inherent tumor-targeting properties and their capacity to deliver therapeutic agents directly to malignant cells. This research delves into the boosted anti-tumor potency of NK-Exos that has been genetically enhanced to overexpress NKG2D, a vital activating receptor, along with interleukin-24 (IL24), a cytokine renowned for its selective suppressive impact on tumor cells. NKG2D facilitates the recognition of tumor cells by binding to stress-induced ligands, while IL24 induces apoptosis and modulates immune responses to enhance tumor destruction. The NK-Exos engineered to express both NKG2D and IL24 significantly enhanced tumor targeting and increased the apoptosis rate of tumor cells by 30% in A549 and by 20% in HELA at 48 h compared with non-modified NK-Exos, respectively. Furthermore, this enhancement also impacted cell proliferation, with inhibition rates increasing by 30%, 15%, and 15% in A549, HELA, and MCF-7 cells, respectively, and it reduced A549 cell migration by 10%. The integration of NKG2D and IL24 within NK-Exos confers a dual therapeutic mechanism, synergistically amplifying their efficacy in cancer treatment. The utility of NK-Exos co-expressing NKG2D and IL24 offers a novel approach to overcome the limitations of current therapies, providing prolonged tumor suppression and precise targeting of malignant cells and holding great promise for clinical application.

Exosomes derived from specific cells may be useful for targeted drug delivery, but tracking them in vivo is essential for their clinical application. However, their small size and complex structure challenge the development of exosome-tracking techniques, and traditional labeling methods are limited by weak affinity and potential toxicity. To address these issues, here we developed a novel bio-orthogonal labeling strategy based on phosphatidylinositol derivatives to fluorescently label exosomes from various human and mouse cell types. The different cell-derived exosomes revealed organ-specific distribution patterns and a favorable safety profile. Notably, 4T1 cell-derived exosomes specifically targeted the lungs. When used as drug carriers loaded with anti-inflammatory resveratrol, these exosomes showed significant therapeutic efficacy in mice with acute respiratory distress syndrome (ARDS), effectively reducing inflammatory responses, mitigating pulmonary fibrosis, and restoring lung tissue morphology and function. Our findings provide a novel exosome labeling strategy and an invaluable tool for their in vivo tracking and targeting screening, while exosomes that specifically target the lungs offer a potential therapeutic strategy for organ-specific diseases such as ARDS.

Extracellular vesicles (EVs) are cell derived nanovesicles which are implicated in both physiological and pathological intercellular communication, including the initiation, progression, and metastasis of cancer. The exchange of biomolecules between stromal cells and cancer cells via EVs can provide a window to monitor cancer development in real time for better diagnostic and interventional strategies. In addition, the process of secretion and internalization of EVs by stromal and cancer cells in the tumor microenvironment (TME) can be exploited for delivering therapeutics. EVs have the potential to provide a targeted, biocompatible, and efficient delivery platform for the treatment of cancer and other diseases. Natural as well as engineered EVs as nanomedicine have immense potential for disease intervention. Here, we provide an overview of current knowledge of EVs' function in cancer progression, diagnostic and therapeutic applications for EVs in the cancer setting, as well as current EV engineering strategies.

Chronic prostatitis is a prevalent urological condition that significantly impacts patients' quality of life. Advances in the study of Extracellular Vesicles (EV) have revealed their close involvement in the pathogenesis of prostatitis. This paper reviews the progress in understanding the role of EV in the pathogenesis of chronic prostatitis type IIIA, particularly their involvement in inflammatory responses, cell signaling, and interactions with immune cells. Additionally, it explores the potential applications of EV as drug delivery vehicles, including the targeted delivery of anti-inflammatory agents and immunomodulators, and highlights the challenges associated with developing exosome-based therapeutic strategies. In-depth research on EV holds promise for offering new insights into the diagnosis and treatment of inflammatory diseases.

Malignant tumors pose a significant threat to human health, and conventional cancer therapies are limited by inadequate targeting, leading to severe side effects. Exosomes, as extracellular vesicles mediating intercellular communication, exhibit advantages such as low immunogenicity, high biocompatibility, and low toxicity. After modification, engineered exosomes can be employed as targeted delivery vehicles in tumor therapy. This review summarizes the cellular origin, production methods, engineering strategies, and drug-loading routes of engineered exosomes, discusses their applications in cancer treatment, and delves into the challenges and issues in translating engineered exosomes to clinical practice, aiming to provide insights for exosome engineering research.

The self-renewal ability and multipotency of stem cells give them great potential for use in wound healing. Stem cell-derived exosomes, owing to their close biological resemblance to their parent cells, offer a more efficient, safer, and economical approach for facilitating cellular communication and interactions within different environments. This potential makes them particularly valuable in the treatment of both acute and chronic wounds, such as lacerations, burns, and diabetic ulcers. Long non-coding RNAs (lncRNAs) enclosed in exosomes, as one of the leading actors of these extracellular microvesicles, through interaction with miRNAs and regulation of various signaling pathways involved in inflammation, angiogenesis, cell proliferation, and migration, could heal the wounds. Exosome-derived lncRNAs from stem cells facilitate extracellular matrix remodeling through interaction between macrophages and fibroblasts. Moreover, alongside regulating the expression of inflammatory cytokines, controlling reactive oxygen species levels, and enhancing autophagic activity, they also modulate immune responses to support wound healing. Regulating the expression of genes and signaling pathways related to angiogenesis, by increasing blood supply and accelerating the delivery of essential substances to the wound environment, is another effect exosomal lncRNAs derived from stem cells for wound healing. These lncRNAs can also enhance skin wound healing by regulating homeostasis, increasing the proliferation and differentiation of cells involved in the wound-healing process, and enhancing fibroblast viability and migration to the injury site. Ultimately, exosome-derived lncRNAs from stem cells offer valuable and novel insights into the molecular mechanisms underlying improved wound healing. They can pave the way for potential therapeutic strategies, fostering further research for a better future. Meanwhile, exosomes derived from mesenchymal stem cells, due to their exceptional regenerative properties, as well as the lncRNAs derived from these exosomes, have emerged as one of the innovative tools in wound healing. This review article aims to narrate the cellular and molecular roles of exosome-derived lncRNAs from stem cells in enhancing wound healing with a focus on mesenchymal stem cells.

Palbociclib, a CDK4/6 inhibitor, plays a crucial role in the treatment of HR+ breast cancer. However, resistance to palbociclib is a significant concern that merits further investigation. Our investigation identifies TMEM45A as a potential driver of palbociclib resistance and its association with increased cellular glycolysis. We demonstrate that TMEM45A is highly expressed in palbociclib-resistant breast cancer (BRCA) cells, correlating with enhanced tumor progression. Silencing TMEM45A enhances sensitivity to palbociclib, promotes cell cycle arrest and apoptosis, and inhibits the proliferation of BRCA cells. Moreover, attenuation of TMEM45A expression reduces cancer aggressiveness by decreasing the expression of EMT and glycolysis-related proteins. Subsequent gene set enrichment analysis (GSEA) confirms that TMEM45A activates the AKT/mTOR signaling pathway, which is integral to cell cycle progression and glycolysis. In a cell line-derived xenograft (CDX) mouse model, TMEM45A knockdown significantly restores sensitivity to palbociclib and suppresses tumor growth. Additionally, the use of engineered exosomes loaded with siRNA targeting TMEM45A presents a promising strategy for enhancing CDK4/6 inhibitor sensitivity without observable toxic side effects in a patient-derived xenograft (PDX) model. Collectively, our findings suggest that TMEM45A may be a therapeutic target for overcoming palbociclib resistance, and exosomal siRNA delivery could be a viable strategy for precision medicine in HR+ breast cancer.

Latexin (LXN) is a secreted protein with a molecular weight of 29 KD, which is considered a tumor suppressor and plays an important role in the inflammatory immune response. LXN is highly expressed in macrophages and regulates macrophage polarity and tumor immune escape, demonstrating excellent clinical potential. However, its mechanism is still unclear. In this study, a macrophage-T cell co-culture system is established to clarify the secretion of macrophage LXN into the extracellular through exosomes. The results indicate that LXN in macrophage-derived exosomes is functional, that is, LXN-enriched exosome inhibits CD4+T cell differentiation into Treg cells in vitro and in vivo, and exhibits good tumor suppressive effects. Based on this discovery, a biomimetic nanoparticle loaded with LXN protein (MØ@LXN-NPS) is designed and synthesized. Furthermore, the MØ@LXN-NPS shows excellent performance in both in vivo and in vitro, especially in enhancing tumor immune surveillance by inhibiting Treg cells in tumor microenvironment, thus exhibiting excellent anti-tumor activity. This study provides a demonstration for the transition of biomolecules from functional research to engineering applications. The excellent performance of MØ@LXN-NPS in tumor immune regulation suggests that the engineered biomimetic nanomedicine has good clinical application prospects.

Secretory autophagy is a classical form of unconventional secretion that integrates autophagy with the secretory process, relying on highly conserved autophagy-related molecules and playing a critical role in tumor progression and treatment resistance. Traditional autophagy is responsible for degrading intracellular substances by fusing autophagosomes with lysosomes. However, secretory autophagy uses autophagy signaling to mediate the secretion of specific substances and regulate the tumor microenvironment (TME). Cytoplasmic substances are preferentially secreted rather than directed toward lysosomal degradation, involving various selective mechanisms. Moreover, substances released by secretory autophagy convey biological signals to the TME, inducing immune dysregulation and contributing to drug resistance. Therefore, elucidating the mechanisms underlying secretory autophagy is essential for improving clinical treatments. This review systematically summarizes current knowledge of secretory autophagy, from initiation to secretion, considering inter-tumor heterogeneity, explores its role across different tumor types. Furthermore, it proposes future research directions and highlights unresolved clinical challenges.

Treatment for bone and joint tuberculosis (BJTB) is challenging due to its refractory and recurrent nature. This study aimed to develop a bioimplantable scaffold with osteoinductive and antituberculosis characteristics to treat BJTB.

This scaffold is built on oxidized hyaluronic acid and carboxymethyl chitosan hydrogel mixed with hydroxyapatite as a bone tissue engineered material. In order to make the scaffold have the biological activity of promoting tissue repair, the engineered exosomes (Exoeng) were added innovatively. In addition, drug-loaded liposomes equipped with an aldehyde group on the surface are cross-linked with the amine group of the hydrogel skeleton to participate in the Schiff base reaction.

The designed scaffold has characteristics of self-healing and injectability exhibit excellent anti-tuberculosis and promoting bone repair activities. Exoeng strongly stimulates cellular angiogenesis and osteogenic differentiation. The liposomes coated in hydrogel can release three kinds of anti-tuberculosis drugs smoothly and slowly, achieving a long term anti-tuberculosis.

The composite bio-scaffold shows good tissue repair and long-term anti-tuberculosis abilities, which expected to provide a viable treatment plan for bone-related BJTB.

Among the most challenging diseases to treat is lung cancer (LC). While immunotherapy has a checkered history, it has lately shown great promise in the treatment of LC, and interest in this promising new approach is on the rise around the globe. Immunotherapy using mesenchymal stem cells (MSCs) is gaining popularity. Regenerative medicine, cell therapy, and immune modulation are three areas that have shown significant interest in MSCs. More than that, MSCs have recently attracted attention as potential anti-cancer drug delivery vehicles due to their inherent ability to go home to tumor locations. Making MSCs a double-edged sword in the fight against neoplastic illnesses, they are also known to impart pro-oncogenic properties. Additionally, multiple studies have proposed extracellular vesicles (EVs) secreted by MSCs as a potential therapeutic agent or method for delivering anti-cancer drugs. However, there has been conflicting evidence regarding the impact of MSCs or MSC-EV on the behavior of cancer cells, and the exact mechanism for this effect is still unknown. Our research has focused on MSCs and their key characteristics, such as their immunomodulatory capabilities for cancer therapy. Our research has also explored the potential of MSCs and their derivatives to treat small-cell and non-small-cell lung cancers (NSCLC and SCLC, respectively) by leveraging MSCs' immunomodulatory characteristics. At the end of this article, we covered the pros and cons of this therapy procedure, as well as what researchers want to do in the future to make it more suitable for clinical application in LC treatment.

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.

The CRISPR-Cas9 technology, one of the groundbreaking genome editing methods for addressing genetic disorders, has emerged as a powerful, precise, and efficient tool. However, its clinical translation remains hindered by challenges in delivery efficiency and targeting specificity. This review provides a comprehensive analysis of the structural features, advantages, and potential applications of various non-viral and stimuli-responsive systems, examining recent progress to emphasize the potential to address these limitations and advance CRISPR-Cas9 therapeutics. We describe how recent reports emphasize that nonviral vectors, including lipid-based nanoparticles, extracellular vesicles, polymeric nanoparticles, gold nanoparticles, and mesoporous silica nanoparticles, can offer diverse advantages to enhance stability, cellular uptake, and biocompatibility, based on their structures and physio-chemical stability. We also summarize recent progress on stimuli-responsive nanoformulations, a type of non-viral vector, to introduce precision and control in CRISPR-Cas9 delivery. Stimuli-responsive nanoformulations are designed to respond to pH, redox states, and external triggers, facilitate controlled and targeted delivery, and minimize off-target effects. The insights in our review suggest future challenges for clinical applications of gene therapy technologies and highlight the potential of delivery systems to enhance CRISPR-Cas9's clinical efficacy, positioning them as pivotal tools for future gene-editing therapies.

Exosomes, small extracellular vesicles secreted by various cells, play crucial roles in the pathogenesis and treatment of oral diseases. Recent studies have highlighted their involvement in orthodontics, periodontitis, oral squamous cell carcinoma (OSCC), and hand, foot, and mouth disease (HFMD). Exosomes have a positive effect on the inflammatory environment of the oral cavity, remodeling and regeneration of oral tissues, and offer promising therapeutic options for bone and periodontal tissue restoration. In OSCC tumor-derived exosomes promote cancer progression through cell proliferation, migration, invasion, and angiogenesis, and serve as potential biomarkers for early diagnosis and prognosis. Additionally, engineered exosomes constructed specifically based on exosome properties hold great promise for targeted drug delivery and regenerative therapies such as bone regeneration in orthodontics and periodontal healing. With continued research, exosomes hold great potential for improving diagnosis and treatment in oral diseases, advancing personalized and regenerative therapies.

Macrophages are innate immune cells present in all tissues and play an important role in almost all aspects of the biology of living organisms. Extracellular vesicles (EVs) are released by cells and transport their contents (micro RNAs, mRNA, proteins, and long noncoding RNAs) to nearby or distant cells for cell-to-cell communication. Numerous studies have shown that macrophage-derived extracellular vesicles (M-EVs) and their contents play an important role in a variety of diseases and show great potential as biomarkers, therapeutics, and drug delivery vehicles for diseases. This article reviews the biological functions and mechanisms of M-EVs and their contents in chronic non-communicable diseases such as cardiovascular diseases, metabolic diseases, cancer, inflammatory diseases and bone-related diseases. In addition, the potential application of M-EVs as drug delivery systems for various diseases have been summarized.

Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of all oral cancers, significantly impacting the survival and quality of life of patients. Exosomes, small extracellular vesicles released by cells, play a crucial role in intercellular communication in cancer. Nevertheless, their function and mechanism in OSCC remain elusive. Search Pubmed, Web of Science, and Cochrane Library using keywords OSCC, exome, diagnosis, and treatment to review the research progress of exome in OSCC. Based on these results, this review starting from the biosynthesis, structure, and contents of exosomes, elaborates on the research progress of exosomes in the diagnosis and treatment of OSCC. It explores the potential of exosomes in the diagnosis and treatment of OSCC, and briefly describes the challenges researchers currently face.

Tumor-cell-derived microparticles (TMPs) have been recognized as chemotherapeutic drug carriers and immunomodulators for anti-tumor therapy. Research in the clinical application of TMPs has been devoted to developing an effective delivery formulation that could enhance their therapeutic effects. Here, we propose thermal-responsive agarose hydrogel microspheres (MTX-TMPs@MSs) with encapsulation of Methotrexate (MTX)-packaging TMPs (MTX-TMPs) and black phosphorus quantum dots (BPQDs) by microfluidic technology for synergistic treatment of malignant ascites. The laden MTX-TMPs, separated from apoptotic tumor cells, could target tumor cells for the delivery of chemotherapy drugs and modulate the tumor immune microenvironment. Under near-infrared (NIR) induced thermal stimulation, MTX-TMPs could be controllably released from the low-melting-point agarose matrix hydrogel microspheres for chemotherapy (CHT) and immunotherapy (IMT). In addition, benefiting from photothermal therapy (PTT)-induced tumor immunogenic death, the anti-tumor immune response triggered by MTX-TMPs was further enhanced. Based on these features, the MTX-TMPs@MSs could remarkably eliminate tumor cells in vitro and obviously suppress tumor growth in vivo through synergistic PTT, CHT, and IMT. Therefore, it is envisaged that this TMPs-integrated microcarrier will have promising applications in clinical tumor therapy. STATEMENT OF SIGNIFICANCE: Primary liver cancer ranks third among the causes of cancer deaths globally, with hepatocellular carcinoma (HCC) being the most common type. In particular, patients with advanced HCC accompanied by malignant ascites, a common complication, indicate tumor metastasis and a poor prognosis. In this paper, we developed stimuli-responsive hydrogel microspheres from microfluidics for the delivery of methotrexate (MTX)-loaded tumor-cell-derived microparticles (MTX-TMPs) for synergistic chemotherapy, photothermal therapy, and immunotherapy. The release of MTX-TMPs from hydrogel microspheres could be on-demand controlled through BPQDs-mediated photothermal stimulus. On the other hand, BPQDs-mediated mild hyperthermia cooperatesss with MTX-TMPs-induced chemotherapy could participate in remodeling the tumor immunosuppressive microenvironment. Thus, the prepared microcarrier system holds great promise for tumor therapy.

Small extracellular vesicles (sEVs) are promising nanocarriers for drug delivery to treat a wide range of diseases due to their natural origin and innate homing properties. However, suboptimal therapeutic effects, attributed to ineffective targeting, limited lysosomal escape, and insufficient delivery, remain challenges in effectively delivering therapeutic cargo. Despite advances in sEV-based drug delivery systems, conventional approaches need improvement to address low drug-loading efficiency and to develop surface functionalization techniques for precise targeting of cells of interest, all while preserving the membrane integrity of sEVs. We report an enhanced gene delivery system using multifunctional sEVs for highly efficient siRNA loading and delivery. The integration of chiral graphene quantum dots enhanced the loading capacity while preserving the structural integrity of the sEVs. Additionally, lysosomal escape is facilitated by functionalizing sEVs with pH-responsive peptides, fully harnessing the inherent homing effect of sEVs for targeted and precise delivery. These sEVs achieved a 1.74-fold increase in cytosolic cargo delivery compared to unmodified sEVs, resulting in substantial gene silencing of around 73%. Our approach has significant potential to advance sEV-based gene delivery in order to accelerate clinical progress.

Nasopharyngeal carcinoma (NPC) is a malignancy arising from the epithelium of the nasopharynx. Given its late diagnosis, NPC raises serious considerations in Southeast Asia. In addition to resistance to conventional treatment that combines chemotherapy and radiation, NPC has high rates of metastasis and frequent recurrence. Exosomes are small membrane vesicles at the nanoscale that transport physiologically active compounds from their source cell and have a crucial function in signal transmission and intercellular message exchange. The exosomes detected in the tissues of NPC patients have recently emerged as a potential non-invasive liquid biopsy biomarker that plays a role in controlling the tumor pathophysiology. Here, we take a look back at what we know so far about the complex double-edged sword role of exosomes in NPC. Exosomes could serve as biomarkers and therapeutic agents, as well as the molecular mechanisms by which they promote cell growth, angiogenesis, metastasis, immunosuppression, radiation resistance, and chemotherapy resistance in NPC. Furthermore, we go over some of the difficulties and restrictions associated with exosome use. It is anticipated that this article would provide the reference for the apply of exosomes in clinical practice.