Chemotherapy is commonly used to manage cancer lesions, but its use is limited or has a high risk of failure due to the side effects of the drugs. The use of a drug delivery system can minimize the side effects of drugs and maximize their anticancer effects. This study investigated the potential of tumor cell-derived small extracellular vesicles (sEV) as drug delivery vehicles for doxorubicin (Dox). In addition, the decoration of vascular endothelial growth factor receptor (VEGFR)-targeting peptide on the sEV provided an enhance specific cancer cell-targeting effect in vitro or homing capacity in vivo. The extrusion method was effective in loading Dox and displaying targeting peptide. The effective Dox release was resulted under acidic condition, an endosome pH. The growth of tumor masses on MCF-7 xenografted mice were significantly inhibited by this drug delivery system. We believe that our results will provide useful information for the development of chemotherapeutic drug delivery systems.

In this review, we comprehensively discuss the application of sEVs miRNAs in ophthalmic diseases by examining their basic characteristics and clinical application potential. Initially, we provide an overview of sEVs, including their definition, source, and functions, while particularly highlighting the importance of miRNAs contained in sEVs and its prospects in the treatment of ocular diseases. Subsequently, the structure and composition of sEVs as well as the biological functions of their encapsulated miRNAs, which expands the current knowledge about their roles in ophthalmic physiology and pathology. In addition, the functions of sEVs miRNAs in the growth of ocular tissues, ocular tissue homeostasis, and common eye diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy, are discussed. The application potential of sEVs miRNAs as diagnostic biomarkers and drug delivery systems for ophthalmic conditions and therapeutic value in diverse eye diseases are explored. Finally, the current challenges affecting research in this field are outlined to provide a basis that guide future utilization of sEVs miRNAs in ophthalmic disease research and clinical management of diverse ophthalmological conditions.

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.

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.

Neurological damage caused by peripheral nerve injury can be devastating and is a common neurological disorder that, along with muscle disorders, reduces the quality of life. Neural crest cells (NCCs) are a transient cell population that occurs during embryogenesis, can differentiate into various cells upon transplantation, and has potential therapeutic effects on neurological diseases. However, there are limitations to cell therapy, such as uncontrolled differentiation and tumor formation. Extracellular vesicles (EVs), which are non-cellular potential therapeutic candidates, are nanosized membrane-bound vesicles. Studies have been reported using starch cells derived from neural cells, such as neural stem cells, because they are involved in cell-to-cell communication and carry a variety of bioactive molecules. We investigated the effects of EVs isolated from NCCs on neuronal cell death and inflammation. Additionally, we overexpressed the nerve growth factor (NGF), which is involved in neural cell growth and proliferation, in NCCs to further investigate the effects of EVs containing NGF. NCCoe-NGF-EVs showed neuroprotective and regenerative properties by modulating inflammatory pathway, promoting Schwann cell activation, and enhancing remyelination. In vitro studies on NCCoe-NGF-EVs suppressed pro-inflammatory cytokines and reduced oxidative stress-induced neuronal apoptosis through NF-κB pathway inhibition and ERK, AKT signal activation. We also evaluated the effect of EVs on neuropathy by performing in vivo study. Our results suggest that NCCoe-NGF-EV had neuroprotective effects by reducing neuronal apoptosis and promoting neuronal proliferation based on neurite outgrowth and anti-inflammation effects treated with NCCoe-NGF-EVs. In addition, NCCoe-NGF-EVs were protected muscle loss caused by peripheral nerve injury. NCCoe-NGF-EV induced regeneration of damaged nerves and inhibited cell death through anti-inflammatory effects. This study suggests the potential of NGF-enriched EVs as non-cellular therapeutic platform for peripheral neuropathies and other neuroinflammatory disorders.

Exosomes have gained increasing attention as robust, biocompatible carriers for targeted therapy. However, current techniques for exosome drug loading suffer from low drug loading efficiency and substantial exosome loss during repeated purification and quantification processes. Here, we present an integrated microfluidic chip (IMC) that streamlines drug loading, separation, and electrochemical detection of exosomes from plasma in a single device. In this design, the three-dimensional (3D) macroporous scaffold and the magnetoresponsive electrode are successfully assembled into the modeling microchip, playing the functions of "3D chaotic flow mixer", "magnetic separator" and "electrochemical detector". When plasma, doxorubicin (DOX), boron clusters and immunomagnetic nanoprobes (IMPs) are simultaneously injected into the IMC, the exosomes are loaded with DOX-boron cluster (EDB) complexes and synchronously recognized by IMPs in the "3D chaotic flow mixer". Our strategy exhibits high DOX loading efficiency owing to the superchaotropic effect of boron clusters and enhanced immunolabeling efficiency by the thorough mixing of the 3D scaffold. Meanwhile, the novel magnetoresponsive electrode enables magnetic separation and real-time, enzyme-linked immunoelectrochemical quantification of exosomes, thereby simplifying the workflow from drug loading to quantification. The resulting EDB in combination with magnetic hyperthermia achieves up to 90% cell-killing efficiency against DOX-resistant breast cancer cells. Overall, our system could simultaneously realize the enhanced DOX loading into exosomes, efficient magnetic immunoseparation of exosomes, and sensitive electrochemical quantification of exosomes, offering a promising approach for autologous exosome-based drug delivery for cancer treatment.

Gastric cancer ranks fifth among the most prevalent cancers globally, with a dismal prognosis. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has emerged as a glimmer of hope for advanced gastric cancer patients. However, not all patients can benefit from this treatment modality, as the tumor microenvironment significantly influences treatment efficacy. Exosomes, pivotal mediators of intercellular communication, exert intricate and diverse effects in shaping and regulating the tumor microenvironment. This review provides a comprehensive overview of the functional mechanisms of exosomes within the gastric cancer tumor microenvironment. It delves into their biogenesis, functions, and impact on innate and adaptive immune cells (such as dendritic cells, myeloid-derived suppressor cells, and T cells) and cancer-associated fibroblasts. Additionally, the potential applications of exosomes in gastric cancer immunotherapy are explored, including their use as biomarkers to predict responses to immune checkpoint inhibitors, and drug delivery vectors, and in the development of exosome-based vaccines and gene therapy. Notably, this review emphasizes the dual nature of exosomes: they can facilitate tumor immune escape, yet they also serve as promising targets for innovative therapeutic strategies. It also compares potential exosome-based strategies with existing immunotherapies like ICIs and emerging CAR-T cell therapies. Finally, insights into the future of exosomes in precision immunotherapy for gastric cancer are offered, presenting a forward-looking perspective on this emerging field.

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.

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.

Exosomes, small membranous vesicles naturally secreted by living cells, have garnered attention for their role in intercellular communication and therapeutic potential. Their low immunogenicity, high biocompatibility, and efficient biological barrier penetration make them promising drug delivery vehicles. This review spans research developments from 2010 to 2025, covering the engineering of exosomes to optimize cargo loading and targeting specificity. We discuss their applications in treating cardiovascular diseases, liver fibrosis, immune diseases, and neurological diseases, alongside ongoing clinical trials and industry progress. Future challenges include scalability, standardization, and minimizing off-target effects. We propose strategies to address these hurdles, such as bioengineering techniques and improved isolation methods. By synthesizing current knowledge and outlining future directions, this review aims to guide researchers toward harnessing exosomes for disease treatment.

The occurrence of antibiotic-resistant bacteria is a serious global health issue, and it emphasizes the need for novel antimicrobial agents. This review explores the potential of snake venom as another alternative strategy against antimicrobial resistance. Snake venoms are complex combinations of bioactive peptides and proteins, including metalloproteases (MPs), serine proteases (SPs), phospholipase A2 (PLA2) enzymes, three-finger toxins (3FTXs), cysteine-rich secretory proteins (CRISPs), L-amino acid oxidases (LAAOs), and antimicrobial peptides (AMPs). The antibacterial products possess wide-spectrum antibacterial activity against resistant microbes via diverse mechanisms such as cell membrane disruption, enzymatic hydrolysis of microbial structures, generation of oxidative stress, inhibition of biofilms, and immunomodulation. Strong antimicrobial activity is reported by most studies, but these are mostly restricted to in vitro testing with low translational use. Although preliminary insights into molecular targets and physiological effects exist, further studies are needed to clarify long-term safety and therapeutic potential. Special attention is given to snake venom-derived extracellular vesicles (SVEVs), which enhance the therapeutic potential of venom toxins by protecting them from degradation, improving bioavailability, and facilitating targeted delivery. Furthermore, innovative delivery strategies such as PEGylation, liposomes, hydrogels, microneedle patches, biopolymer films, and nanoparticles are discussed for their role in reducing systemic toxicity and enhancing antimicrobial efficacy. The rational modification of venom-derived peptides further expands their therapeutic utility by improving pharmacokinetics and minimizing off-target effects. Together, these approaches highlight the translational potential of snake venom-based therapies as next-generation antimicrobials in the fight against resistant infections. By outlining these challenges and directions, this review positions snake venom as an overlooked but fertile resource in the battle against antibiotic resistance.

Skin diseases are a broad category of diseases and each has complex conditions, which makes it challenging for dermatologists to provide targeted treatment. Exosomes are natural vesicles secreted by cells and play a key role in cell communication. Due to their unique characteristics, including inherent stability, minimal immunogenicity, high biocompatibility, and exceptional ability to penetrate cells, exosomes are being explored as potential delivery vehicles for therapeutics across various diseases including skin problems. Utilizing exosomes for drug delivery in skin diseases can improve treatment outcomes and reduce the side effects of traditional drug delivery methods. Indeed, exosomes can be engineered or utilized as an innovative approach to deliver therapeutic agents such as small molecule drugs, genes, or proteins specifically to affected skin cells. In addition to targeting specific skin cells or tissues, these engineered exosome-based nanocarriers can reduce off-target effects and improve drug efficacy. Hence, this article highlights the transformative potential of this technology in revolutionizing drug delivery in dermatology and improving 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.

Chronic wounds pose a significant healthcare challenge, impacting millions of patients worldwide and burdening healthcare systems substantially. These wounds often occur as comorbidities and are prone to infections. Such infections hinder the healing process, complicating clinical management and proving recalcitrant to therapy. The environment within the wound itself poses challenges such as lack of oxygen, restricted blood flow, oxidative stress, ongoing inflammation, and bacterial presence. Traditional systemic treatment for such chronic peripheral wounds may not be effective due to inadequate blood supply, resulting in unintended side effects. Furthermore, topical applications are often impervious to persistent biofilm infections. A growing clinical concern is the lack of effective therapeutic modalities for treating chronic wounds. Additionally, the chemically harsh wound microenvironment can reduce the effectiveness of treatments, highlighting the need for drug delivery systems that can deliver therapies precisely where needed with optimal dosages. Compared to cell-based therapies, exosome-based therapies offer distinct advantages as a cell-free approach for chronic wound treatment. Exosomes are of endosomal origin and enable cell-to-cell communications, and they possess benefits, including biocompatibility and decreased immunogenicity, making them ideal vehicles for efficient targeting and minimizing off-target damage. However, exosomes are rapidly cleared from the body, making it difficult to maintain optimal therapeutic concentrations at wound sites. The hydrogel-based approach and development of biocompatible scaffolds for exosome-based therapies can be beneficial for sustained release and prolong the presence of these therapeutic exosomes at chronic wound sites. Engineered exosomes have been shown to possess stability and effectiveness in promoting wound healing compared to their unmodified counterparts. Significant progress has been made in this field, but further research is essential to unlock their clinical potential. This review seeks to explore the benefits and opportunities of exosome-based therapies in chronic wounds, ensuring sustained efficacy and precise delivery despite the obstacles posed by the wound environment.

Exosomes, which are nano-sized natural vesicles secreted by cells, are crucial for intercellular communication and interactions, playing a significant role in various physiological and pathological processes. Their characteristics, such as low toxicity and immunogenicity, high biocompatibility, and remarkable drug delivery capabilities-particularly their capacity to traverse the blood-brain barrier-make exosomes highly promising vehicles for drug administration in the treatment of brain disorders. This review provides a comprehensive overview of exosome biogenesis and isolation techniques, strategies for the drug loading and functionalization of exosomes, and exosome-mediated blood-brain barrier penetration mechanisms, with a particular emphasis on recent advances in exosome-based drug delivery for brain disorders. Finally, we address the opportunities and challenges associated with utilizing exosomes as a drug delivery system for the brain, summarizing the barriers to clinical translation and proposing future research directions.

This study introduces advanced nanoparticle-based drug delivery systems (NDDS) designed for targeted colorectal cancer treatment. We developed and characterized three distinct formulations: Bevacizumab-loaded chitosan nanoparticles (BEV-CHI-NP), polymeric micelles (BEV-PM), and BEV-conjugated exosomes enriched with AS1411 and N1-methyladenosine (AP-BEV + M1A-EXO). Each formulation exhibited optimized physicochemical properties, with particle sizes between 150 and 250 nm and surface charges ranging from + 14.4 to + 43 mV, ensuring stability and targeted delivery. The AP-BEV + M1A-EXO formulation demonstrated targeted delivery to VEGF, a protein commonly overexpressed in colorectal cancer cells, as indicated by localized staining. This suggests a more precise delivery of the therapeutic agent to VEGF-enriched regions. In contrast, the BEV-CHI-NP formulation exhibited a broader pattern of tumor suppression, evidenced by reduced overall staining intensity. The BEV-PM group showed moderate effects, with a relatively uniform protein expression across tumor tissues. In vivo studies indicated that the AP-BEV + M1A-EXO formulation achieved a notable reduction in tumor volume (~ 65.4%) and decreased levels of tumor biomarkers, including CEA and CA 19-9, compared to conventional BEV-API treatment. In vitro experiments using human colon tumor organoids (HCTOs) further supported these findings, showing a significant reduction in cell viability following exposure to AP-BEV + M1A-EXO. These results suggest that combining aptamer specificity with exosome-based delivery systems could enhance the precision and effectiveness of colorectal cancer therapies, representing a potential advancement in treatment strategies. In vivo experiments further revealed that the AP-BEV + M1A-EXO formulation outperformed conventional BEV-API treatment, achieving a four-fold increase in tumor suppression. This formulation resulted in a 65.4% reduction in tumor volume and a significant decrease in tumor biomarkers, including CEA and CA 19-9. In vitro studies also demonstrated a significant reduction in cell viability in human colon tumor organoids exposed to AP-BEV + M1A-EXO. These findings highlight the potential of combining aptamer specificity with exosome-based delivery systems to enhance the precision and efficacy of colorectal cancer therapies, marking a promising step forward in cancer treatment innovation.

High-dose methotrexate (HD-MTX) serves as the cornerstone of central nervous system lymphoma (CNSL) treatment, but its efficacy is limited due to low blood-brain barrier (BBB) penetration and adverse effects. This study is focused on an exosome-based drug delivery approach aimed at enhancing BBB permeability, thereby reducing the required dosage of methotrexate (MTX) while ensuring specific targeting of CNSL.

Human adipose-derived mesenchymal stem cells (hAMSCs) were modified with a lentiviral vector encoding anti-CD19, incorporated into exosomes characterized by colloidal gold immunoelectron microscopy and Nano flow cytometry. MTX loaded into anti-CD19-Exos via co-incubation, assessed for loading and encapsulation efficiencies using HPLC. In vitro BBB model constructed using hCMEC/D3 and astrocytes to investigate BBB permeability. In vivo efficacy of anti-CD19-Exo-MTX evaluated in intracranial CNSL models using MRI. Biodistribution tracked with DiR-labeled exosomes, drug concentration in CSF measured by HPLC. LC-MS/MS identified and characterized exosomal proteins analyzed using GO Analysis. Neuroprotective effects of exosomal proteins assessed with TUNEL and Nissl staining on hippocampal neurons in CNSL models. Liver and kidney pathology, blood biochemical markers, and complete blood count evaluated exosomal protein effects on organ protection and MTX-induced myelosuppression.

We generated anti-CD19-Exo derived from hAMSCs. These adapted exosomes effectively encapsulated MTX, enhancing drug accessibility within lymphoma cells and sustained intracellular accumulation over an extended period. Notably, anti-CD19-Exo-MTX interacted with cerebrovascular endothelial cells and astrocytes of the BBB, leading to endocytosis and facilitating the transportation of MTX across the barrier. Anti-CD19-Exo-MTX outperformed free MTX in vitro, exhibiting a more potent lymphoma-suppressive effect (P < 0.05). In intracranial orthotopic CNSL models, anti-CD19-Exo-MTX exhibited a significantly reduced disease burden compared to both the MTX and Exo-MTX groups, along with prolonged overall survival (P < 0.05). CSF drug concentration analysis demonstrated enhanced stability and longer-lasting drug levels for anti-CD19-Exo-MTX. Anti-CD19-Exo-MTX exhibited precise CNSL targeting with no organ toxicity. Notably, our study highlighted the functional potential of reversal effect of hAMSCs-exosomes on MTX-induced neurotoxicity, hepatic and renal impairment, and myelosuppression.

We present anti-CD19-Exo-MTX as a promising exosome-based drug delivery platform that enhances BBB permeability and offers specific targeting for effective CNSL treatment with reduced adverse effects.

Nanotechnology, based on the utilization of nanoparticles, has revolutionized drug delivery techniques, offering groundbreaking methods for managing and diagnosing intricate ailments over the past four decades. This article aims to underscore how the use of these particles has been used to treat previously incurable diseases such as cancer, Alzheimer's, and Parkinson's disease. Recently, the integration of diagnostic imaging and targeted therapy using theranostic nanoparticles has improved cancer treatment precision. Moreover, exosome-based drug delivery has demonstrated high in vivo biocompatibility and antigen-carrying ability during vaccine development. The unique properties of these tiny particles enable their transport to specific locations inaccessible to large drug molecules. The development of these nanodrugs by either encapsulation or adsorption of drugs on particles has allowed the loading of both hydrophilic and hydrophobic drugs. Innovative engineering approaches have enabled the engineering of shear-sensitive nanoparticles for site-targeted drug release, which eliminates the requirement for frequent doses, which is common in conventional drug delivery. Factors such as size, shape as well as surface modification are considered during the top-down and bottom-up approaches for engineering nanoparticle-based systems. However, issues related to scaling up manufacturing, long-term safety, and regulatory approval for these techniques must be resolved. The use of these drug delivery systems offers many therapeutic advantages. This article examines the application of these systems across various medical domains including cancer treatment, infectious diseases, cardiovascular disorders, central nervous system ailments, and ophthalmic conditions. This fusion of nanotechnology with drug delivery has the potential to elevate healthcare standards in the future by introducing innovative frameworks for revolutionizing therapeutic practices.

Oxaliplatin (OXA) is the first-line drug for the treatment of colorectal cancer (CRC), and susceptibility to drug resistance affects patient prognosis. However, the exact underlying mechanisms remain unclear. Platinum-acquired resistance in CRC is a continuous transition process; though, current research has mainly focused on the end state of drug resistance, and the early events of drug resistance have been ignored. In this study, single-cell transcriptome sequencing is combined with a dynamic network biomarker (DNB), and found that the functional inhibition of the mitochondrial electron transport chain complex I occur early in the development of attained resistance to OXA in CRC cells, as evidenced by a decrease in the levels of subunit proteins, primarily NDUFB8. Specifically, the mouse double minute 2 homologue (MDM2) mediates the ubiquitination and degradation of NDUFB8, reducing intracellular reactive oxygen species (ROS) generation under chemotherapeutic stress, consequently contributing to drug resistance. Based on this, the study constructs engineered extracellular vesicles carrying siMDM2 by electroporation and validates the application of EV-siMDM2 to improve the efficacy of OXA-based chemotherapy by inhibiting the MDM2/NDUFB8/ROS signaling axis in patient-derived xenograft (PDX) and hepatic and pulmonary metastasis mouse models, thus providing new ideas and an experimental basis for the platinum-resistant treatment of CRC.

Infection occurs when pathogens penetrate tissues, reproduce, and trigger a host response to both the infectious agents and their toxins. A diverse array of pathogens, including viruses and bacteria, can cause infections. The host's immune system employs several mechanisms to combat these infections, typically involving an innate inflammatory response. Inflammation is a complex biological reaction that can affect various parts of the body and is a key component of the response to harmful stimuli. Sepsis arises when the body's response to infection leads to widespread damage to tissues and organs, potentially resulting in severe outcomes or death. The initial phase of sepsis involves immune system suppression. Early identification and targeted management are crucial for improving sepsis outcomes. Common treatment approaches include antibiotics, intravenous fluids, blood cultures, and monitoring urine output. This study explores the potential of exosome therapy in enhancing the management and alleviation of sepsis symptoms.

Cancer, a significant cause of mortality, necessitates improved drug delivery strategies. Exosomes, as natural drug carriers, offer a more efficient, targeted, and less toxic drug delivery system compared to direct dispersal methods via ingestion or injection. To be successfully implemented as drug carriers, efficient loading of drugs into exosomes is crucial, and a deeper understanding of the loading mechanism remains to be solved. This study introduces surface-enhanced Raman scattering (SERS) to monitor drug loading efficacy at the single vesicle level. By enhancing the Raman signal, SERS overcomes limitations in Raman spectroscopy. A gold nanopyramids array-based SERS substrate assesses exosome heterogeneity in drug-loading capabilities with the help of single-layer graphene for precise quantification. This research advances targeted drug delivery by presenting a more efficient method of evaluating drug-loading efficiency into individual exosomes through SERS-based monitoring. Furthermore, the study explores leveraging osmotic pressure variations, enhancing the efficiency of drug loading into exosomes.

Exosomes derived from cancer cells significantly influence the tumor immune microenvironment and can limit the efficacy of immunotherapy. However, the impact of exosomes on B cell-dependent anti-tumor immunity remains poorly understood. Here, we demonstrate that exosomes secreted by MC38 (MC38-Exos), a murine colorectal cancer cell line, induce B cells to adopt immunosuppressive phenotypes. MC38-Exos inhibits B cell proliferation and survival. Additionally, MC38-Exos induce B cells to acquire characteristics of regulatory B cells, including the upregulation of IL-10 and TGF-β. Finally, B cells treated with MC38-Exos impair the functional efficacy of CD8+ T cells. Transcriptome analysis reveals that MC38-Exos markedly suppresses gene pathways associated with B cell receptor (BCR) signaling, as well as antigen processing and presentation in B cells, but up-regulates genes involving apoptosis pathway. Mechanistically, NF-κB pathway was enriched in KEGG analysis, and was validated by western blot. Finally, inhibition of MC38-Exo in vivo activates B-cell mediated anti-tumor immunity. Thus, MC38-Exo has a profound effect of transcriptome of B cells and attenuates B cell-dependent anti-tumor immunity, supporting the rationale for targeted exosome therapy in human colorectal cancer.

Rotator cuff injury (RCI), characterized by shoulder pain and restricted mobility, represents a subset of tendon-bone insertion injuries (TBI). In the majority of cases, surgical reconstruction of the affected tendons or ligaments is required to address the damage. However, numerous clinical failures have underscored the suboptimal outcomes associated with such procedures. Further investigations have revealed that these failures are largely attributable to delayed healing at the tendon-bone interface, excessive formation of vascularized scar tissue, and inadequate integration of tendon grafts within bone tunnels. As a result, the healing process of rotator cuff injuries faces significant challenges.Bone marrow-derived mesenchymal stem cell exosomes (BMSC-exos) have emerged as a prominent focus of research within the field of bioengineering, owing to their remarkable potential to regulate cellular proliferation and differentiation, modulate immune responses, and facilitate tissue repair and regeneration following cellular damage. In this review, we explore the anti-inflammatory, angiogenic, anti-scarring, and bone metabolism-modulating effects of BMSC-exos in the context of rotator cuff injury. Additionally, we address the limitations and ongoing challenges within current research, offering insights that could guide the clinical application of BMSC-exos in the treatment of rotator cuff injuries in the future.

Exosomes are small extracellular vesicles of endocytic origin released by various cell types. They consist of lipid bilayers containing macromolecules such as lipids, proteins, microRNAs, growth factors, cytokines, and carbohydrates. Exosomes play a critical role in the diagnosis and treatment of various diseases. For instance, exosome contents have been utilized as biomarkers in body fluids (urine, saliva, serum) to identify cancers, autoimmune diseases, and inflammatory conditions such as sepsis. Due to their small size and ability to reach tumor microenvironments, exosomes are also used as carriers for chemotherapeutic drugs in drug delivery systems. Furthermore, evidence indicates that malignant cells release exosomes into the tumor microenvironment, influencing immune cells in a paracrine manner. Additionally, immune cell-derived exosomes, such as those from Natural Killer (NK) cells or cytotoxic T lymphocytes (CTLs), show potential as therapeutic agents in treating malignancies like leukemia. This review discusses the diagnostic role of exosomes in various hematological malignancies and explores the therapeutic potential of immune cell-derived exosomes in these diseases.

Extracellular vesicles (EVs) have emerged as promising tools in diagnostics and therapy for chronic diseases, including cancer and Alzheimer's. Small EVs, also called exosomes, are lipid-bound particles (≈30-150 nm) that play a role in healthy and pathophysiological interactions, including intercellular communication, by transporting bioactive molecules, including proteins, lipids, and nucleic acids. Their ability to cross biological barriers, such as the blood-brain barrier, makes them ideal candidates for targeted therapeutic interventions. In the context of chronic diseases, exosomes can be engineered to deliver active agents, including small molecules and siRNAs to specific target cells, providing a novel approach to precision medicine. Moreover, exosomes show great promise as repositories for diagnostic biomarkers. Their cargo can reflect the physiological and pathological status of the parent cells, making them valuable indicators of disease progression and response to treatment. This paper presents a comprehensive review of the application of exosomes in four chronic diseases: cancer, cardiovascular disease, neurodegenerative disease, and orthopedic disease, which significantly impact global public health due to their high prevalence and associated morbidity and mortality rates. Furthermore, the potential of exosomes as valuable tools for theranostics and disease management is highlighted. Finally, the challenges associated with exosomes and their demonstrated potential for advancing future nanomedicine applications are discussed.

Heart failure (HF) represents a cardiovascular disease that significantly threatens global well-being and quality of life. Electroactive nanomaterials, characterized by their distinctive physical and chemical properties, emerge as promising candidates for HF prevention and management. This review comprehensively examines electroactive nanomaterials and their applications in HF intervention. It presents the definition, classification, and intrinsic characteristics of conductive, piezoelectric, and triboelectric nanomaterials, emphasizing their mechanical robustness, electrical conductivity, and piezoelectric coefficients. The review elucidates their applications and mechanisms: 1) early detection and diagnosis, employing nanomaterial-based sensors for real-time cardiac health monitoring; 2) cardiac tissue repair and regeneration, providing mechanical, chemical, and electrical stimuli for tissue restoration; 3) localized administration of bioactive biomolecules, genes, or pharmacotherapeutic agents, using nanomaterials as advanced drug delivery systems; and 4) electrical stimulation therapies, leveraging their properties for innovative pacemaker and neurostimulation technologies. Challenges in clinical translation, such as biocompatibility, stability, and scalability, are discussed, along with future prospects and potential innovations, including multifunctional and stimuli-responsive nanomaterials for precise HF therapies. This review encapsulates current research and future directions concerning the use of electroactive nanomaterials in HF prevention and management, highlighting their potential to innovating in cardiovascular medicine.

Esophageal cancer (EC) is one of the most common malignant tumors worldwide. Exosomes are a type of extracellular vesicles produced by eukaryotic cells and present in all body fluids. Recent studies have revealed that exosomes can be used as a tool for cell signaling and have great potential in cancer diagnosis and treatment strategies. This article reviews the research progress of exosomes in EC in recent years, mainly including the mechanism of action, diagnostic markers, therapeutic targets, and drug carriers. The challenges faced are discussed to provide guidelines for further research in future.

Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining neural homeostasis but can also contribute to disease and injury when this state is disrupted or conversely play a pivotal role in neurorepair. One way that microglia exert their effects is through the secretion of small vesicles, microglia-derived exosomes (MGEVs). Exosomes facilitate intercellular communication through transported cargoes of proteins, lipids, RNA, and other bioactive molecules that can alter the behavior of the cells that internalize them. Under normal physiological conditions, MGEVs are essential to homeostasis, whereas the dysregulation of their production and/or alterations in their cargoes have been implicated in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), spinal cord injury (SCI), and traumatic brain injury (TBI). In contrast, MGEVs may also offer therapeutic potential by reversing inflammation or being amenable to engineering for the delivery of beneficial biologics or drugs. The effects of MGEVs are determined by the phenotypic state of the parent microglia. Exosomes from anti-inflammatory or pro-regenerative microglia support neurorepair and cell survival by delivering neurotrophic factors, anti-inflammatory mediators, and molecular chaperones. Further, MGEVs can also deliver components like mitochondrial DNA (mtDNA) and proteins to damaged neurons to enhance cellular metabolism and resilience. MGEVs derived from pro-inflammatory microglia can have detrimental effects on neural health. Their cargo often contains pro-inflammatory cytokines, molecules involved in oxidative stress, and neurotoxic proteins, which can exacerbate neuroinflammation, contribute to neuronal damage, and impair synaptic function, hindering neurorepair processes. The role of MGEVs in neurodegeneration and injury-whether beneficial or harmful-largely depends on how they modulate inflammation through the pro- and anti-inflammatory factors in their cargo, including cytokines and microRNAs. In addition, through the propagation of pathological proteins, such as amyloid-beta and alpha-synuclein, MGEVs can also contribute to disease progression in disorders such as AD and PD, or by the transfer of apoptotic or necrotic factors, they can induce neuron toxicity or trigger glial scarring during neurological injury. In this review, we have provided a comprehensive and up-to-date understanding of the molecular mechanisms underlying the multifaceted role of MGEVs in neurological injury and disease. In particular, the role that specific exosome cargoes play in various pathological conditions, either in disease progression or recovery, will be discussed. The therapeutic potential of MGEVs has been highlighted including potential engineering methodologies that have been employed to alter their cargoes or cell-selective targeting. Understanding the factors that influence the balance between beneficial and detrimental exosome signaling in the CNS is crucial for developing new therapeutic strategies for neurodegenerative diseases and neurotrauma.

Cellulose nanocrystals (CNCs), derived from diverse sources and distinguished by their inherent biodegradability, excellent biocompatibility, and facile cellular engulfment due to their rod-like structure, hold great promise as carriers for the development of nano-delivery systems. In this work, highly efficient rod-like CNCs were employed as substrates for grafting glycidyl onto their surfaces through ring-opening polymerization, forming hyperbranched polymers with superior cell uptake properties. Subsequently, 4-vinylbenzeneboronic acid (VB) and poly (ethylene glycol) methyl ether methacrylate (PEGMA) were employed as monomers in the polymerization process to fabricate a pH-responsive targeted nano-delivery system, denoted as CNCs-VB-PEGMA, via single electron transfer reactive radical polymerization (SET-LRP) reaction. The CNCs-VB-PEGMA was successfully prepared and used for the loading of curcumin (Cur) to form a pH-responsive nano-delivery system (CNCs-VB-PEGMA-Cur), and the loading rate of Cur was as high as 70.0 %. Studies showed that this drug delivery system could actively targeting liver cancer cells with the 2D cells model and 3D tumor microsphere model, showing efficient liver cancer cell-killing ability. Collectively, the CNCs-VB-PEGMA drug delivery system has potential applications in liver cancer therapy as an actively targeting and pH-responsive drug delivery system.

Burn injuries are serious injuries that have a big impact on a person's health and can even cause death. Incurring severe burns can incite an immune response and inflammation within the body, alongside metabolic changes. It is of utmost importance to grasp the fact that the effects of the burn injury extend beyond the body, affecting the mind and overall well-being. Burn injuries cause long-lasting changes that need to be taken care of in order to improve their quality of life. The intricate process of skin regeneration at the site of a burn wound involves a complex and dynamic interplay among diverse cells, growth factors, nerves, and blood vessels. Exciting opportunities have arisen in the field of stem cells and regenerative medicine, allowing us to explore the development of cell-free-based alternatives that can aid in the treatment of burn injuries. These cell-free-based therapies have emerged as a promising facet within regenerative medicine. Exosomes, also referred to as naturally occurring nanoparticles, are small endosome-derived vesicles that facilitate the delivery of molecular cargo between the cells, thus allowing intercellular communication. The knowledge gained in this field has continued to support their therapeutic potential, particularly in the domains of wound healing and tissue regeneration. Notably, exosomes derived from mesenchymal stem cells (MSCs) can be safely administered in the system, which is then adeptly uptaken and internalized by fibroblasts/epithelial cells, subsequently accelerating essential processes such as migration, proliferation, and collagen synthesis. Furthermore, exosomes released by immune cells, specifically macrophages, possess the capability to modulate inflammation and effectively diminish it in adjacent cells. Exosomes also act as carriers when integrated with a scaffold, leading to scarless healing of cutaneous wounds. This comprehensive review examines the role of exosomes in burn wound healing and their potential utility in regeneration and repair.

Recently, the incidence of brain diseases, such as central nervous system degenerative diseases, brain tumors, and cerebrovascular diseases, has increased. However, the blood-brain barrier (BBB) limits the effective delivery of drugs to brain disease areas. Therefore, the mainstream direction of new drug development for these diseases is to engineer drugs that can better cross the BBB to exert their effects in the brain. This paper reviews the research progress and application of the main trans-BBB drug delivery strategies (receptor/transporter-mediated BBB crossing, focused ultrasound to open the BBB, adenosine agonist reversible opening of the BBB, aromatic resuscitation, transnasal administration, cell-mediated trans-BBB crossing, and viral vector system-mediated brain drug delivery). Meanwhile, the potential applications, advantages, and disadvantages of these strategies for crossing the BBB are analyzed. Finally, the future development prospects of strategies for crossing the BBB are also discussed. These strategies have potential value for treating brain diseases.

Exosomes, membrane-enveloped vesicles found in various cell types, including Wharton's jelly mesenchymal stem cells, play a crucial role in intercellular communication and regulation. Their use as a cell-free nanotechnology and drug delivery system has attracted attention. Triple-negative breast cancer (TNBC) is a major global health problem and is characterized by a high mortality rate. This study investigates the potential of Wharton's Jelly mesenchymal stem cell-derived exosomes (WJ-Exo) as carriers of S3I-201 and their effects on STAT3 expression in breast cancer cell lines, and evaluates whether these exosomes can enhance the anti-tumor effect of S3I-201.

The filtered WJ-Exos were analyzed by Transmission Electron Microscopy (TEM), Scanning electron microscopy (SEM), Dynamic Light Scattering (DLS), flow cytometry, and Western blotting. These exosomes were then used for loading with S3I-201, resulting in the nano-formulation WJ-Exo(S3I-201). The effect of WJ-Exo(S3I-201) on 4T1 cancer cells was investigated in vitro using MTT assay, flow cytometry, wound healing assay, Western blotting and Quantitative Real-Time Polymerase chain reaction (qPCR) analysis. Finally, the therapeutic efficacy of the nano-formulation was investigated in vivo using a tumor-bearing mouse model.

In vitro experiments showed that co-incubation of 4T1 cells with the nano-formulation resulted in a significant reduction in p-STAT3 levels, induction of apoptosis, modulation of Bcl-2, Bax and caspase-3 protein and gene expression, and inhibition of migration. In vivo, treatment of tumor-bearing mice with WJ-Exo(S3I-201) showed a strong antitumor effect that exceeded the efficacy observed in the S3I-201 group.

Our results demonstrate that WJ-Exo is an effective carrier for targeting S3I-201 to tumor cells and enhances the therapeutic efficacy of S3I-201 in tumor-bearing mice.

Ischemic stroke is the fourth leading cause of adult disability in the US, and it is a huge social burden all over the world. However, the efficient treatment of ischemic stroke is not available. An apparent reason for failing to find or develop an intervention for ischemic stroke is contributed to the tight blood-brain barrier (BBB). The unique characteristics of exosomes that can traverse BBB have been highlighted among researchers investigating interventions for ischemic stroke conditions. Additionally, intermittent hypoxic training has been considered a potential intervention in the treatment or rehabilitation process of ischemic stroke patients. In this mini-review, we are going to review the possibility of applying exosomes produced by a subject who does intermittent hypoxic conditioning in a treatment program for ischemic stroke.

Following spinal cord injury, the inflammatory environment at the injury site causes local microglia and astrocytes to activate, which worsens the nerve damage in the affected area. Quercetin, an anti-inflammatory agent, has been limited in spinal cord injury due to its poor water solubility and easy degradation. Stem cell-derived extracellular vesicles can go through the blood-brain barrier and are an ideal drug delivery system. In this study, umbilical cord mesenchymal stem cell-derived extracellular vesicles were used to load quercetin to prevent its degradation and allow it to accumulate at the site of spinal cord injury. Our results showed that quercetin-loaded extracellular vesicles could inhibit the activation of microglia to M1 phenotype through the TLR4/NF-κB pathway, and the activation of astrocytes to A1 phenotype through the JAK2/STAT3 pathway. This reduced the production of inflammatory factors, mitigated neuronal damage, and inhibited the growth of astroglial scar, but promoted the recovery of motor function in rats with spinal cord injury.

Personalized medicine is a new approach to modern oncology. Here, to facilitate the application of extracellular vesicles (EVs) derived from lung cancer cells as potent advanced therapy medicinal products in lung cancer, the EV membrane was functionalized with a specific ligand for targeting purposes. In this role, the most effective heptapeptide in binding to lung cancer cells (PTHTRWA) was used. The functionalization process of EV surface was performed through the C- or N-terminal end of the heptapeptide. To prove the activity of the EVs functionalized with PTHTRWA, both a model of lipid membrane mimicking normal and cancerous cell membranes as well as human adenocarcinomic alveolar basal epithelial cells (A549) and human normal bronchial epithelial cells (BEAS-2B) have been exposed to these bioconstructs. Magnetic resonance imaging (MRI) showed that the as-bioengineered PTHTRWA-EVs loaded with superparamagnetic iron oxide nanoparticle (SPIO) cargos reach the growing tumor when dosed intravenously in NUDE Balb/c mice bearing A549 cancer. Molecular dynamics (MD) in silico studies elucidated a high affinity of the synthesized peptide to the α5β1 integrin. Preclinical safety assays did not evidence any cytotoxic or genotoxic effects of the PTHTRWA-bioengineered EVs.

Extracellular vesicles (EVs) hold great promise for clinical application as new diagnostic and therapeutic modalities. This paper describes major GMP-based upstream and downstream manufacturing processes for EV large-scale production, also focusing on post-processing technologies such as surface bioengineering and uploading studies to yield novel EV-based diagnostics and advanced therapy medicinal products. This paper also focuses on the quality, safety, and efficacy issues of the bioengineered EV drug candidates before first-in-human studies. Because clinical trials involving extracellular vesicles are on the global rise, this paper encompasses different clinical studies registered on clinical-trial register platforms, with varying levels of advancement, highlighting the growing interest in EV-related clinical programs. Navigating the regulatory affairs of EVs poses real challenges, and obtaining marketing authorization for EV-based medicines remains complex due to the lack of specific regulatory guidelines for such novel products. This paper discusses the state-of-the-art regulatory knowledge to date on EV-based diagnostics and medicinal products, highlighting further research and global regulatory needs for the safe and reliable implementation of bioengineered EVs as diagnostic and therapeutic tools in clinical settings. Post-marketing pharmacovigilance for EV-based medicinal products is also presented, mainly addressing such topics as risk assessment and risk management.

Extracellular vesicles (EVs) contribute to the development of cancer in various ways. Non-Hodgkin lymphoma (NHL) is a cancer of mature lymphocytes and the most common hematological malignancy globally. The most common form of NHL, diffuse large B-cell lymphoma (DLBCL), is primarily treated with chemotherapy, autologous stem cell transplantation (ASCT), and/or chimeric antigen receptor T-cell (CAR-T) therapy. With NHL disease progression and its treatment, extracellular vesicles play remarkable roles in influencing outcomes. This finding can be utilized for therapeutic intervention to improve patient outcomes for NHL. This review focuses on the multifaceted roles of EVs with NHL and its potential for guiding patient care.

Contemporary trends reveal an escalating interest in regenerative medicine-based interventions for addressing refractory skin defects. Conventional wound healing treatments, characterized by high costs and limited efficacy, necessitate a more efficient therapeutic paradigm to alleviate the economic and psychological burdens associated with chronic wounds. Mesenchymal stem/stromal cells (MSCs) constitute cell-based therapies, whereas cell-free approaches predominantly involve the utilization of MSC-derived extracellular vesicles or exosomes, both purportedly safe and effective. Exploiting the impact of MSCs by paracrine signaling, exosomes have emerged as a novel avenue capable of positively impacting wound healing and skin regeneration. MSC-exosomes confer several advantages, including the facilitation of angiogenesis, augmentation of cell proliferation, elevation of collagen production, and enhancement of tissue regenerative capacity. Despite these merits, challenges persist in clinical applications due to issues such as poor targeting and facile removal of MSC-derived exosomes from skin wounds. Addressing these concerns, a three-dimensional (3D) platform has been implemented to emend exosomes, allowing for elevated levels, and constructing more stable granules possessing distinct therapeutic capabilities. Incorporating biomaterials to encapsulate MSC-exosomes emerges as a favorable approach, concentrating doses, achieving intended therapeutic effectiveness, and ensuring continual release. While the therapeutic potential of MSC-exosomes in skin repair is broadly recognized, their application with 3D biomaterial scenarios remains underexplored. This review synthesizes the therapeutic purposes of MSCs and exosomes in 3D for the skin restoration, underscoring their promising role in diverse dermatological conditions. Further research may establish MSCs and their exosomes in 3D as a viable therapeutic option for various skin conditions.

This study investigates the intricate interplay between environmental pollutants and exosomes, shedding light on a novel paradigm in environmental health and disease. Cellular stress, induced by environmental toxicants or disease, significantly impacts the production and composition of exosomes, crucial mediators of intercellular communication. The heat shock response (HSR) and unfolded protein response (UPR) pathways, activated during cellular stress, profoundly influence exosome generation, cargo sorting, and function, shaping intercellular communication and stress responses. Environmental pollutants, particularly lipophilic ones, directly interact with exosome lipid bilayers, potentially affecting membrane stability, release, and cellular uptake. The study reveals that exposure to environmental contaminants induces significant changes in exosomal proteins, miRNAs, and lipids, impacting cellular function and health. Understanding the impact of environmental pollutants on exosomal cargo holds promise for biomarkers of exposure, enabling non-invasive sample collection and real-time insights into ongoing cellular responses. This research explores the potential of exosomal biomarkers for early detection of health effects, assessing treatment efficacy, and population-wide screening. Overcoming challenges requires advanced isolation techniques, standardized protocols, and machine learning for data analysis. Integration with omics technologies enhances comprehensive molecular analysis, offering a holistic understanding of the complex regulatory network influenced by environmental pollutants. The study underscores the capability of exosomes in circulation as promising biomarkers for assessing environmental exposure and systemic health effects, contributing to advancements in environmental health research and disease prevention.

Chronic kidney disease (CKD) affects more than 10% of the global population, and its incidence is increasing, partially due to an increase in the prevalence of disease risk factors. Acute kidney injury (AKI) is an independent risk factor for CKD and end-stage renal disease (ESRD). The pathogenic mechanisms of CKD provide several potential targets for its treatment. However, due to off-target effects, conventional drugs for CKD typically require high doses to achieve adequate therapeutic effects, leading to long-term organ toxicity. Therefore, ideal treatments that completely cure the different types of kidney disease are rarely available. Several approaches for the drug targeting of the kidneys have been explored in drug delivery system research. Nanotechnology-based drug delivery systems have multiple merits, including good biocompatibility, suitable degradability, the ability to target lesion sites, and fewer non-specific systemic effects. In this review, the development, potential, and limitations of low-molecular-weight protein-lysozymes, polymer nanomaterials, and lipid-based nanocarriers as drug delivery platforms for treating AKI and CKD are summarized.