International Journal Of Nanomedicine[JOURNAL]
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200 papers
From Bench to Bedside: Multifunctional Nanoplatforms in the Fight Against Non-alcoholic Fatty Liver Disease.
Zhao Y, Wang L, Zhu S … +2 more , Feng R, Zhang W
Int J Nanomedicine · 2026 · PMID 42094738 · Full text
Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population and represents a major public health burden, characterized by disease progression from steatosis to non-alcoholic steatoh...
Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of the global adult population and represents a major public health burden, characterized by disease progression from steatosis to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma. Despite this high prevalence and serious clinical outcomes, no pharmacologic therapies are currently approved, and standard lifestyle interventions often prove ineffective. Therefore, there is a major unmet clinical need for innovative treatments. To overcome these limitations, nanomedicine has emerged as a promising approach, with multifunctional nanoplatforms (MFNs) demonstrating distinctive advantages in tackling the complex pathology of NAFLD. For instance, MFNs enable targeted liver delivery, synergistic therapeutic effects (eg, reducing hepatic lipogenesis and fibrosis), and theranostic integration, thereby minimizing rapid clearance and adverse effects associated with conventional low-molecular-weight compounds. Consequently, this review comprehensively synthesizes the latest advances in MFNs for NAFLD management, critically analyzing their design strategies (eg, nanoencapsulation of bioactive compounds for enhanced bioavailability) and mechanistic roles in ameliorating inflammation, fibrosis, and steatosis. Furthermore, it explores challenges such as optimizing organ-specific targeting and personalized applications, while outlining future research directions to accelerate clinical translation and address coexisting conditions like chronic hepatitis B infection. By bridging current knowledge gaps, this work aims to inform the development of effective nanotherapeutic strategies for NAFLD.
Nanomaterial-Mediated Targeting of Mitochondrial Metabolism: Strategies and Applications in Cancer Therapy.
Hu Y, Xie P, Li J … +4 more , Liu R, Wang H, Wang Z, Liu C
Int J Nanomedicine · 2026 · PMID 42094737 · Full text
Mitochondria serve as cellular powerhouses and function as central hubs for oxidative metabolism and signaling regulation. These organelles produce ATP primarily through oxidative phosphorylation (OXPHOS), thereby fuelin...
Mitochondria serve as cellular powerhouses and function as central hubs for oxidative metabolism and signaling regulation. These organelles produce ATP primarily through oxidative phosphorylation (OXPHOS), thereby fueling cellular growth and function. In cancer, metabolic reprogramming drives malignant progression, with mitochondria playing a pivotal role. To meet heightened energy and biosynthetic demands, cancer cells modulate mitochondrial OXPHOS activity while enhancing fatty acid oxidation and amino acid metabolism, thereby maintaining redox balance and supporting survival and proliferation. Targeting mitochondrial metabolism with nanomaterials has emerged as a promising strategy for cancer therapy. This review covers advances from 2018-2025, encompassing lipid-based, polymeric, peptide-functionalized, and stimuli-responsive nanocarriers. By employing nanocarriers to deliver metabolic inhibitors or chemotherapeutic agents precisely to mitochondria, this approach can disrupt energy metabolism, impair redox homeostasis, or induce apoptosis in tumor cells. Such targeted intervention not only enhances chemotherapy efficacy but also synergizes with radiotherapy and immunotherapy, offering a potential route to overcome resistance. Despite its considerable promise, several challenges remain in the nanomaterial-based targeting of mitochondrial metabolism, including optimization of targeting efficiency and biosafety. Future efforts should focus on refining these aspects to accelerate the clinical translation of precise mitochondrial metabolism-directed therapies.
Microenvironment-Activated Fe-MOF Nanoplatform Enables Controlled Doxorubicin Release and Ferroptosis-Associated Oxidative Damage in MCF-7 Breast Cancer Cells.
Yuan M, Wu Y, Zheng J … +5 more , Wang C, Wang J, Zheng Y, Wang Y, Wang B
Int J Nanomedicine · 2026 · PMID 42094736 · Full text
INTRODUCTION: Doxorubicin (DOX) is a cornerstone chemotherapeutic for breast cancer; however, its clinical efficacy is limited by inefficient intracellular delivery and dose-limiting off-target toxicity. Microenvironment...
INTRODUCTION: Doxorubicin (DOX) is a cornerstone chemotherapeutic for breast cancer; however, its clinical efficacy is limited by inefficient intracellular delivery and dose-limiting off-target toxicity. Microenvironment-responsive nanoplatforms offer a promising strategy to enhance tumor selectivity and therapeutic performance. METHODS: A core-shell nanosystem (UTMD) was constructed by coating an NH-MIL-88B(Fe) metal-organic framework (Fe-MOF) shell onto a UCNP@TiO scaffold. The Fe-MOF shell was designed as a dual pH- and glutathione (GSH)-responsive gatekeeper for controlled DOX release. The nanosystem was characterized for structural features, drug loading, and stimulus-responsive release behavior. Cellular uptake, intracellular trafficking, cytotoxicity, and redox-related biochemical changes were evaluated in MCF-7 breast cancer cells and HEK-293 normal cells. RESULTS: UTMD achieved high encapsulation efficiency (86.5%) and maintained stability under physiological conditions, while enabling accelerated DOX release in acidic and reducing environments. The nanosystem enhanced cellular internalization and promoted nuclear accumulation of DOX in MCF-7 cells. In addition, UTMD induced significant intracellular redox imbalance, characterized by GSH depletion, increased reactive oxygen species levels, and elevated lipid peroxidation, accompanied by mitochondrial membrane potential depolarization. These changes are consistent with ferroptosis-associated oxidative damage. Compared with free DOX, UTMD exhibited improved cytocompatibility in HEK-293 cells. DISCUSSION: The Fe-MOF shell functions as a microenvironment-responsive gatekeeper that coordinates controlled drug release with iron-mediated oxidative stress. This integrated design links chemotherapy with ferroptosis-associated mechanisms, improving therapeutic selectivity and mechanistic interpretability. CONCLUSION: UTMD represents a microenvironment-activated nanoplatform that enables controlled DOX delivery and ferroptosis-associated oxidative damage. This strategy enhances antitumor efficacy while reducing off-target toxicity, offering potential for improved breast cancer therapy.
Recent Advances in Novel Drug Delivery Systems for the Management of Cutaneous Squamous Cell Carcinoma.
Fu X, Zhang Z, Dong Q … +8 more , Li S, Wang X, Zhang H, Bai J, Han H, Shi L, Zheng K, Liang L
Int J Nanomedicine · 2026 · PMID 42088400 · Full text
Cutaneous squamous cell carcinoma (cSCC) is a type of cancer that originates from the growth of skin cells. It represents the second most common form of non-melanoma skin cancer and primarily arises from the malignant pr...
Cutaneous squamous cell carcinoma (cSCC) is a type of cancer that originates from the growth of skin cells. It represents the second most common form of non-melanoma skin cancer and primarily arises from the malignant proliferation of keratinocytes in the epidermis or skin appendages. The global incidence of cSCC is increasing, and its onset is primarily associated with prolonged exposure to ultraviolet radiation, genetic susceptibility, and immunosuppression. These factors severely impair patients' quality of life and skin health. Conventional therapeutic strategies for cSCC mainly rely on surgery, radiotherapy, or photodynamic therapy. Although these approaches are widely applied in clinical practice, they present several limitations, including high recurrence rates, poor suitability for special populations, and significant toxic side effects. To overcome these shortcomings, researchers worldwide have recently conducted extensive studies on novel therapeutic approaches. Among them, innovative drug delivery systems have emerged as a highly promising research direction. Unlike traditional treatments, these new drug delivery systems, including nanocarriers (liposomes, polymeric nanoparticles, inorganic nanoparticles), microneedle arrays, hyaluronic acid-based carriers, and DNA nanocomposites, can precisely deliver therapeutic agents to cSCC lesions, reduce systemic toxicity, and achieve sustained drug release at the tumor site. These advantages make them an optimal option for cSCC therapy. This study provides a comprehensive summary of recent advances in the design, functional performance, and translational prospects of these novel delivery technologies. It particularly elucidates how they overcome the limitations of conventional therapies and offer new possibilities for developing effective treatment strategies for cSCC.
How Selective are Nanomaterials to Treat Osteoarthritis.
Zhang Y, Cheng X, Tian J … +6 more , Liu J, Teng Y, Chen J, Wu Z, Ding H, Zhang Z
Int J Nanomedicine · 2026 · PMID 42088399 · Full text
Osteoarthritis (OA) is now increasingly recognized as a disease that affects the entire joint, where synovial inflammation plays a key role in pain, cartilage degeneration, and structural progression. Synovial macrophage...
Osteoarthritis (OA) is now increasingly recognized as a disease that affects the entire joint, where synovial inflammation plays a key role in pain, cartilage degeneration, and structural progression. Synovial macrophages (SMs) are key regulators in this process due to their phenotypic plasticity and central roles in amplifying inflammation, disrupting immunometabolism, and interacting with other joint-resident cells. These characteristics make SMs attractive targets for disease-modifying interventions. However, conventional therapies are limited by poor intra-articular retention, low cellular selectivity, and inadequate control over complex pathogenic networks. This review summarizes the biological functions of SMs in OA and explains why they are a mechanistically important and therapeutically accessible target. Next, we provide a structured overview of nanomaterial-based strategies for SM-targeted OA therapy, covering major material platforms, receptor-guided delivery approaches, subset- and state-selective targeting, intracellular functional intervention, and multi-target combination designs. We highlight representative studies that show how nanomedicines can improve local retention, enhance macrophage-specific uptake, and modulate inflammation, metabolism, oxidative stress, and cell fate. Finally, we discuss the major barriers to clinical translation, such as macrophage heterogeneity, safety, pharmacokinetics, and chemistry, manufacturing, and controls (CMC), and outline future directions for biomarker-guided and precision nanotherapy in OA.
Advancements in Neonatal Brain Injury Treatment: Nanomedicine-Based Strategies.
Jin P, He C, Zhang X … +1 more , Huang Y
Int J Nanomedicine · 2026 · PMID 42088398 · Full text
Neonatal brain injury, such as hypoxic-ischemic encephalopathy (HIE), is a leading cause of infant mortality and long-term neurodevelopmental disabilities. Current clinical therapeutic strategies are limited by the blood...
Neonatal brain injury, such as hypoxic-ischemic encephalopathy (HIE), is a leading cause of infant mortality and long-term neurodevelopmental disabilities. Current clinical therapeutic strategies are limited by the blood-brain barrier (BBB), the complexity of the injury cascade, and the narrow therapeutic window. Nanomedicine has shown potential in preclinical studies for overcoming these barriers by leveraging its unique nanoscale characteristics and engineerability design to load, stabilize, and deliver vulnerable biomacromolecules across the compromised BBB to the lesion site. This review presents the first systematic horizontal comparison and critical evaluation of the major nanoplatforms employed in neonatal brain injury therapy. Based on data derived primarily from animal models, we analyze the heterogeneity across studies in model systems, administration routes, and efficacy endpoints, revealing common challenges in the field regarding long-term safety, manufacturability, and reproducibility. This review aims to provide guidance for selecting appropriate nanoplatforms to facilitate the translational advancement of this field toward clinical applications.
Plant-Derived Nanovesicles: Resolving Conceptual Confusion, Overcoming Isolation Challenges, and Advancing Translational Potential.
Zhang Z, Chen G, Zheng K … +6 more , Lin M, Zheng D, Lu Y, Huang L, Chen X, Gan R
Int J Nanomedicine · 2026 · PMID 42088397 · Full text
Plant-derived nanovesicles (PDNVs) are promising bioactive nanoparticles with potential in drug delivery, immune regulation, and tissue repair. However, inconsistent terminology and isolation methods hinder reproducibili...
Plant-derived nanovesicles (PDNVs) are promising bioactive nanoparticles with potential in drug delivery, immune regulation, and tissue repair. However, inconsistent terminology and isolation methods hinder reproducibility and clinical translation. A key confusion lies in their comparison with plant extracellular vesicles (PEVs), which are naturally secreted, whereas PDNVs are typically extracted by breaking plant tissues. This process yields a mix of extracellular and intracellular vesicles, creating both functional diversity and challenges. The heterogeneity complicates standardization, large-scale production, and quality control. Here, we clarify the distinctions between PDNVs and PEVs, and then we explore key factors that affect PDNVs isolation. These include the type of plant used, how the plant is processed, and how the vesicles are purified. We highlight workflow-specific optimizations that boost PDNV recovery (e.g. 4-5 fold higher yields with optimized PEG precipitation) and enhance purity (e.g. ATPS delivering multi-fold higher recovery while eliminating >95% of protein contaminants). Finally, we propose strategies to help establish standardized methods for using PDNVs in biomedical applications.
Research Progress on Nanoformulations Based on Active Components from Traditional Chinese Medicine for MASLD.
Gou ZX, Li NW, Yao JY … +1 more , Wang YL
Int J Nanomedicine · 2026 · PMID 42088396 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease with rising prevalence and disease burden. However, despite recent therapeutic advances, effective and broadly applicable treatm...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic liver disease with rising prevalence and disease burden. However, despite recent therapeutic advances, effective and broadly applicable treatment options remain limited, prompting continued efforts to develop novel therapeutic agents. Traditional Chinese Medicine (TCM) has attracted growing interest in MASLD management because its bioactive compounds can target multiple pathogenic processes. However, many TCM-derived compounds are limited by poor solubility, low bioavailability, and insufficient tissue specificity. Nanotechnology-based formulations enable controlled release and targeted delivery, offering a strategy to improve the utilization and therapeutic efficacy of TCM-derived active ingredients against MASLD. Based on a structured literature search across four databases, 45 representative studies were included and narratively synthesized according to nanoplatform type, design features, and mechanism-related therapeutic actions. Compared with previous broader reviews on TCM nanomedicine or MASLD-related nanotherapies, this review particularly emphasizes MASLD-oriented TCM nanoformulations from the perspectives of platform classification, design features, and mechanism-related therapeutic actions. We also discuss current challenges and future directions for clinical translation.
Promoter-Driven Nanodrugs Suppress BIRC5-Positive Cancers Independent of ABCB1 Status and IDO1 Expression.
Chang YC, Huang WL, Su WC … +3 more , Leung E, Cheng FY, Cheung CHA
Int J Nanomedicine · 2026 · PMID 42088395 · Full text
INTRODUCTION: BIRC5 (survivin), an inhibitor of apoptosis protein, is overexpressed in most tumors and is associated with drug resistance, proliferation, and metastasis, while being largely undetectable in normal differe...
INTRODUCTION: BIRC5 (survivin), an inhibitor of apoptosis protein, is overexpressed in most tumors and is associated with drug resistance, proliferation, and metastasis, while being largely undetectable in normal differentiated tissues. This unique expression pattern makes BIRC5 an exceptionally selective therapeutic target, offering the potential to maximize anticancer efficacy while minimizing systemic toxicity to healthy tissues. However, few BIRC5-targeted agents have advanced to late-stage clinical trials. METHODS: We developed two nanodrug formulations using poly-L-lysine-modified NH-FeO magnetite nanoparticles (PL-MNPs) for selective targeting of BIRC5-positive cancer cells. We further evaluated their anti-cancer efficacy in vitro and in vivo (zebrafish xenograft model), using cancer cell models that expressed BIRC5 and exhibited ABCB1-mediated drug resistance and IDO1-induced immune therapy insensitivity. RESULTS: The PL-MNPs delivered plasmids driven by the promoter (p) encoding either antisense mRNA (As-) or a dominant-negative BIRC5 protein (dN-BIRC5), for tumor-specific BIRC5 inhibition. These nanodrugs demonstrated robust in vitro and in vivo anti-cancer activity in multiple BIRC5-positive cell lines (MIA PaCa-2, NTUB1, NTU0.017, SK-OV-3, KB, and KB-TAX50). The activity was preserved across cancer types and independent of ABCB1-mediated drug resistance, while maintaining cancer cell specificity, and was not affected by IDO1 expression, a factor associated with poor responses to immune therapy. PL-MNP uptake was partially mediated by clathrin-dependent endocytosis, with acidic intracellular environments facilitating efficient plasmid release. Conjugation of nanoparticles with Herceptin (trastuzumab) significantly increased cellular uptake and anticancer activity, especially in clathrin-deficient SK-BR-3 cells that overexpress ERBB2. CONCLUSION: These findings establish that the easily synthesized PL-MNP-p/As- and PL-MNP-p/dN-BIRC5 nanodrugs have strong potential to overcome BIRC5- and ABCB1-related drug resistance, representing a broadly applicable strategy against various malignancies. While the size of our nanodrug (~400 nm in hydrodynamic diameter) is compatible with reported effective nanoparticle sizes in some models, the extent to which the enhanced permeability and retention (EPR) effect contributes to tumor accumulation in human cancers remains uncertain and will require validation in more clinically relevant models and imaging modalities.
Application and Advances of Cell Membrane-Coated Nanoparticles in Diabetic Wound Healing.
Sui X, Li X, Zhang P … +3 more , Sun X, Zhao Y, Yuan X
Int J Nanomedicine · 2026 · PMID 42079439 · Full text
Wound healing in diabetes is a complicated and challenging task, which is affected by many factors. For example, microcirculatory disorders, inflammatory reactions, cell signaling disruption, abnormal fibrosis, and impai...
Wound healing in diabetes is a complicated and challenging task, which is affected by many factors. For example, microcirculatory disorders, inflammatory reactions, cell signaling disruption, abnormal fibrosis, and impaired immunity due to high blood sugar may have an adverse effect on wound healing. In order to address this problem, researchers have continued to explore a broad range of innovative approaches. Nanoparticles, as a novel repair material, are widely used due to their unique physical and chemical properties, particularly in the treatment of diabetes; however, they also have certain limitations. Cell membrane-coated nanoparticles, with their inherent biocompatibility and precise drug delivery capabilities, have emerged as a novel and highly effective strategy for treating diabetic wounds. Among these, nanoparticles coated with macrophage membranes and mesenchymal stem cell membranes have demonstrated the most significant therapeutic effects in wound anti-inflammation, vascular regeneration, and tissue repair. They can effectively improve the local pathological microenvironment, offering a novel and highly effective nanotherapeutic strategy for the treatment of chronic wounds. This paper systematically reviews research progress on nanoparticles coated with red blood cell membranes, macrophage membranes, stem cell membranes, and exosome membranes for treating diabetic wounds. It comprehensively organizes findings based on membrane source classification, mechanisms of action and in vitro/in vivo evidence. Compared to existing reviews, this paper's primary innovations and contributions lie in establishing a comprehensive membrane classification system, deeply analyzing the synergistic logic of multi-mechanism actions, and it provides a comprehensive analysis of practical challenges in areas such as reproducibility, safety, immunomodulation, large-scale production, regulatory compliance, and clinical translation. It provides theoretical support and practical references for developing more precise and safer wound repair strategies in the future.
Evaluation of Self-Illuminating Nanoconjugates Against Pancreatic Ductal Adenocarcinoma.
Abal-Sanisidro M, Ruiz-Cañas L, Batres-Ramos S … +7 more , Blanco MG, García-Bermejo ML, García-Fernández J, Rodríguez-Cobo L, López-Higuera JM, Sainz B, de la Fuente M
Int J Nanomedicine · 2026 · PMID 42079438 · Full text
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer-related mortality by 2030, underscoring the need for new therapeutic approaches. While photodynamic therapy (...
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second leading cause of cancer-related mortality by 2030, underscoring the need for new therapeutic approaches. While photodynamic therapy (PDT) has proven to be efficient for treating superficial solid tumors, conventional laser-dependent PDT is limited by poor tissue penetration. To address this challenge, we developed a novel self-illuminating nanoconjugate platform (SI-NCs) capable of activating PDT without external light. METHODS: We engineered SI-NCs composed of the bioluminescent enzyme RLuc8 conjugated to quantum dots (QDots 705) to generate internal light for activating the FDA-approved photosensitizer verteporfin. We then evaluated SI-NC photophysical properties and assessed their ability to induce localized antitumor activity in PDAC models. RESULTS: SI-NCs were successfully synthesized and characterized, demonstrating efficient bioluminescence resonance energy transfer and activation of verteporfin. In vitro studies in immortalized pancreatic cancer cell lines and patient-derived primary cultures revealed the mechanism of action and confirmed antitumor efficacy of bioluminescent-activated PDT. CONCLUSION: In vivo testing in patient-derived xenograft (PDX) models validated the therapeutic potential of SI-NCs, supporting this self-illuminating platform as a promising strategy to overcome light-penetration barriers and enhance PDT for PDAC treatment.
Decoy Nanoparticles and Protein Corona Modulation: A Novel Frontier in Sepsis Treatment.
Denisova ER, Volkova DS, Streltsova VV … +12 more , Kopytov SA, Krivosheev AS, Panfilova EV, Yan N, Kostyushev D, Ganjalikhani-Hakemi M, Pokrovsky VS, Lopus M, Golovin AV, Zamyatnin AA, Celia C, Parodi A
Int J Nanomedicine · 2026 · PMID 42079437 · Full text
Sepsis remains a major global health challenge due to its complex pathophysiology and limited therapeutic options. Nanomedicine offers innovative strategies to address these limitations by enabling diverse nanoparticle d...
Sepsis remains a major global health challenge due to its complex pathophysiology and limited therapeutic options. Nanomedicine offers innovative strategies to address these limitations by enabling diverse nanoparticle designs and mechanisms that modulate the septic response. This review examines the dynamic interactions between nanoparticles and the immune system, with a focus on how protein corona formation shapes nanoparticle behavior, biodistribution, and therapeutic efficacy. Disease-specific protein corona profiles can serve as pathology "fingerprints" for diagnosis and targeted delivery, and their controlled formation is now emerging as a therapeutic tool rather than only a diagnostic readout. While the protein corona is a spontaneous biomolecular layer, its composition can be rationally steered to support defined therapeutic goals. In this context, decoy nanoparticles are engineered to sequester pathogens or inflammatory mediators, such as cytokines, histones, and neutrophil extracellular traps, thereby mitigating inflammation and tissue damage. This review discusses how protein corona engineering can potentiate decoy strategies in sepsis diagnosis and therapy, highlighting key platforms including macrophage‑like nanoparticles that neutralize endotoxins and cytokines, histone‑binding hydrogels, and mesoporous silica nanoparticles that scavenge cell‑free DNA and inhibit Toll‑like receptor activation. We also address how Artificial Intelligence can improve prediction of protein corona dynamics and identification of disease‑specific protein signatures, enabling more personalized nanodecoy design. Given the highly dynamic and heterogeneous nature of sepsis, characterized by evolving circulating mediators and protein profiles, integrating protein corona control with decoy mechanisms offers a multifaceted route to limit immune dysregulation, enhance drug delivery, and reduce organ damage, paving the way toward precision nanomedicine in sepsis.
Design and Application of Multiscale Systems and Scaffolds Based on Functional Polymeric Materials in Treating Chemoradiotherapy-Induced Oral Mucositis.
Pi C, Qin G, Zhang F … +5 more , Ren Y, Luo M, Wang D, Bai G, Zhang Q
Int J Nanomedicine · 2026 · PMID 42079436 · Full text
Chemoradiotherapy-induced oral mucositis (OM) is prevalent and complication in patients with head and neck cancers, characterized by mucosal erythema, erosion, and ulceration. OM not only causes severe pain, significantl...
Chemoradiotherapy-induced oral mucositis (OM) is prevalent and complication in patients with head and neck cancers, characterized by mucosal erythema, erosion, and ulceration. OM not only causes severe pain, significantly impairs patients' quality of life, but may also disrupt the overall cancer treatment regimen. The complex and dynamic oral microenvironment presents a major challenge for effective OM management, while current clinical strategies remain limited in lack efficient drug delivery systems. In this context, functional polymeric materials have emerged as promising platforms for OM prevention and treatment due to their biocompatibility and adaptability to the oral microenvironment. This review systematically outlines the pathological changes in the oral microenvironment following radiotherapy or chemotherapy and discusses how these alterations impede conventional therapies. We then highlight recent advances in functional polymeric materials-based devices designed to target the pathological microenvironment for enhanced drug delivery and mucosal regeneration. Finally, we discuss the translational challenges and future directions of material-based strategies for OM, aiming to inform the development of more precise and effective approaches.
Bacterial Extracellular Vesicles in Aging: Mechanisms and Therapeutic Prospects.
Tan J, Zubair M, Zhang L … +5 more , Liu L, Li K, Wang Y, Yan Y, Xu W
Int J Nanomedicine · 2026 · PMID 42079435 · Full text
Bacterial extracellular vesicles (bEVs) are increasingly recognized as critical mediators of gut-host interactions; however, their specific role in the aging process remains obscured by fragmented data and disease-specif...
Bacterial extracellular vesicles (bEVs) are increasingly recognized as critical mediators of gut-host interactions; however, their specific role in the aging process remains obscured by fragmented data and disease-specific silos. Current understanding lacks a cohesive mechanism that explains how age-related physiological changes transform bEVs from commensal signals into systemic drivers of pathology. This review synthesizes disparate findings to elucidate a synergistic mechanism: aging compromises intestinal barrier integrity, facilitating bEV translocation, while simultaneously impairing immune clearance capabilities (e.g. loss of Vsig4+ Kupffer cells), leading to their toxic accumulation. We resolve conflicting reports on bEV functionality-such as the paradoxical pro-calcific effects of GG-derived vesicles in chronic kidney disease-by contextualizing them within the host's aging microenvironment. Beyond mapping these interactions across the gut-brain, metabolic, cardiovascular, and bone axes, we identify specific cargo molecules, such as lipopolysaccharide (LPS), curli, and bacterial DNA, that fuel inflammaging. However, translating these insights into therapeutic applications faces significant challenges, including methodological heterogeneity in isolation protocols and unresolved immunogenicity risks. By outlining a strategic roadmap for standardization and rigorous clinical validation, this study redefines bEVs not merely as biomarkers but as actionable targets for delaying aging and mitigating age-related diseases.
-Derived Extracellular Vesicles Alleviate Inflammatory Bowel Disease by Inhibiting the NF-κB/NLRP3 Pathway.
Miao R, Wang S, Yin H … +7 more , Zhu R, Yin Y, Liao W, Wang S, Zhang J, Li R, Xu J
Int J Nanomedicine · 2026 · PMID 42079434 · Full text
BACKGROUND: Plant-derived extracellular vesicles (PDEV) are emerging as natural nanomedicines for various diseases. () is a traditional Chinese herb long used to treat intestinal inflammatory bowel disorders (IBD), with...
BACKGROUND: Plant-derived extracellular vesicles (PDEV) are emerging as natural nanomedicines for various diseases. () is a traditional Chinese herb long used to treat intestinal inflammatory bowel disorders (IBD), with its therapeutic effects attributed to bioactive flavonoids such as baicalin and wogonin. However, whether SEV contribute to its anti-inflammatory activity remains unexplored. The assembled multi-component nature of SEV, which carry flavonoids, lipids, proteins, and miRNAs, suggests a potential to exert therapeutic effects against IBD through mechanisms distinct from isolated compounds, with potential advantages in bioavailability and multi-target engagement. METHODS: We demonstrated that SEV exert potent antioxidant and anti-inflammatory effects in LPS-stimulated RAW264.7 macrophages and Caco-2 intestinal epithelial cells. Moreover, we assessed the therapeutic effects of SEV on dextran sulfate sodium (DSS)-induced IBD in a murine model. RESULTS: In inflamed RAW264.7, SEV modulated the NF-κB/NLRP3 signaling axis to exert anti-inflammatory effects. They scavenged reactive oxygen species (ROS), restored mitochondrial membrane potential, upregulated the anti-inflammatory cytokine IL-10, and suppressed the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. In Caco-2 intestinal epithelial cells, SEV also repaired intestinal barrier function by restoring expression of the tight junction proteins Zonula Occludens-1 (ZO-1), Claudin-1, and Occludin (OCLN), alongside reduced TNF-α levels. In vivo, SEV accumulated at colonic inflammatory loci to effectively alleviate IBD, as evidenced by improved body weight and increased colon length. This protective effect was mediated through inhibition of the NF-κB/NLRP3 signaling axis in colon tissues, which subsequently restored intestinal barrier integrity by increasing goblet cell numbers, upregulating OCLN proteins, and enhancing Mucin2 (MUC2) secretion, while simultaneously rebalancing inflammatory cytokines through suppression of TNF-α/IL-1β and promotion of IL-10 production. CONCLUSION: SEV have the potential to protect the colon against DSS-induced colitis by inhibiting the NF-κB/NLRP3 signaling pathway, providing a promising therapeutic candidate for IBD.
Harnessing Nanocarriers to Improve Psychiatric Treatment: Progress, Limitations, and Future Directions.
Ge X, Zhao L, Xing X … +3 more , Hao Y, Zhang Z, Sun G
Int J Nanomedicine · 2026 · PMID 42063535 · Full text
To address clinical bottlenecks of traditional antipsychotic drugs, including delayed onset of action, significant peripheral side effects, and poor patient compliance, nanodelivery systems offer a feasible approach thro...
To address clinical bottlenecks of traditional antipsychotic drugs, including delayed onset of action, significant peripheral side effects, and poor patient compliance, nanodelivery systems offer a feasible approach through their unique physicochemical properties to improve drug solubility, optimize in vivo transport, and enhance blood-brain barrier (BBB) penetration efficiency. This review focuses on the application potential and translational value of nanodelivery systems in psychiatric disorders. We systematically summarize recent advances in the construction strategies of mainstream nanocarriers, including lipid‑based, polymer‑based, inorganic nanomaterials, Metal-Organic Frameworks (MOFs), and Extracellular Vesicles (EVs), as well as commonly used nanoparticle preparation and characterization techniques. We briefly discuss key challenges facing nanoformulations, such as long‑term safety, large‑scale production, and batch‑to‑batch consistency, and highlight future directions driven by artificial intelligence and precision medicine. This review aims to provide insights for the rational design of nanodelivery systems for psychiatric disorders and to advance the development of precision psychiatry.
Nanotherapy for Pancreatitis: From Single-Cell Targeting Toward Multicellular-Coordinated Regulation.
Li BF, Li XH, Deng Y … +2 more , Deng J, Zhang XM
Int J Nanomedicine · 2026 · PMID 42052517 · Full text
Pancreatitis constitutes a serious global health challenge characterized by a multicellular pathogenesis and limited therapeutic options. The recent discovery of different cellular pathogenic mechanisms and the emerging...
Pancreatitis constitutes a serious global health challenge characterized by a multicellular pathogenesis and limited therapeutic options. The recent discovery of different cellular pathogenic mechanisms and the emerging effectiveness of nanotechnology-based, cell-targeted therapies have provided promising therapeutic avenues for pancreatitis. However, the identification of effective cellular targets, the elucidation of nanotherapeutic mechanisms, and the multicellular-coordinated modulation remain fragmented and insufficiently defined. Here, we summarize recent progress in understanding pathogenic mechanisms from the perspective of different cell populations and analyze relevant nanotechnology-based approaches designed to target these cells in detail. By bridging different cellular pathogenesis with advances in nanotherapeutic design, this review offers a clear framework for cell-targeted nanotherapeutics across the disease progression, proposing pathological and methodological insights to guide the future development of multicellular-coordinated nanomedicines for pancreatitis.
Research on the Inhibition of Cancer Cell Metastasis by Graphene Oxide Suppresses the Translation of the Snail mRNA.
Wei X, Luo C, Ming X … +7 more , Jia X, Long P, Feng L, Zhu M, Hu X, Li M, Li H
Int J Nanomedicine · 2026 · PMID 42052516 · Full text
INTRODUCTION: Lung cancer is the most common malignant tumor worldwide and often presents with advanced metastasis. This study explores the effects of graphene oxide (GO) on lung cancer cell motility, investigates underl...
INTRODUCTION: Lung cancer is the most common malignant tumor worldwide and often presents with advanced metastasis. This study explores the effects of graphene oxide (GO) on lung cancer cell motility, investigates underlying mechanisms, and identifies potential therapeutic targets. METHODS: The effects of GO on the viability and motility of lung cancer cells A549 and H226, and normal bronchial epithelial cells BEAS-2B, were assessed using cytotoxicity, scratch, and Transwell assays. Mechanisms were explored by measuring intracellular ROS, EMT-related and TGF-β pathway protein expression, cellular TGF-β release, and Snail mRNA levels, suggesting potential new targets. RESULTS: Cytotoxicity, scratch, and Transwell experiments indicated that GO had cytotoxic effects on A549, H226, and BEAS-2B, and the effects increased with increasing GO concentration and culture time. A specific concentration of GO could significantly inhibit the cell motility of A549 and H226 within a specific time window. The results of the molecular mechanism experiment showed that within the selected GO concentration and time window, there was no significant change in intracellular reactive oxygen species (ROS); the epithelial-associated protein E-cadherin increased, the EMT regulatory protein Snail decreased, the level of TGF-β secreted by cells did not change, and the expression level of Snail mRNA increased. CONCLUSION: GO increases Snail mRNA but suppresses its translation, reducing EMT protein Snail and increasing E-cadherin, which further decreases tumor cell motility, offering a novel therapeutic strategy for addressing distant metastasis in lung cancer.
Nanotechnology-Assisted Co-Delivery of Immunotherapeutic Agents for Targeting Ovarian Cancer: Prospects and Challenges.
Jiao L, Li M, Tan M … +3 more , Zheng L, Liu Y, Cao Y
Int J Nanomedicine · 2026 · PMID 42052515 · Full text
BACKGROUND: Ovarian cancer is one of the most lethal gynecologic malignancies, mainly due to late diagnoses and chemoresistance. The immune checkpoint inhibitors and other immunotherapies achieve very low response rates...
BACKGROUND: Ovarian cancer is one of the most lethal gynecologic malignancies, mainly due to late diagnoses and chemoresistance. The immune checkpoint inhibitors and other immunotherapies achieve very low response rates in ovarian cancer. Nanotechnology-assisted co-delivery can helpful by simultaneously delivering multiple therapeutic agents together with their collective advantages. METHODS: This review documents recent advances in nanocarrier-based co-delivery of immunotherapeutics for ovarian cancer, including organic (liposomes, Polymeric nanoparticles, dendrimers), inorganic (gold nanoparticles, mesoporous silica nanoparticles, and metal-organic frameworks), and hybrid (polymer-drug conjugates combined with gene vectors, polymer-lipid nanoparticles) nanocarrier systems. Early clinical trial data show that such systems can reprogram the myeloid cells in ovarian cancer. Key co-delivery strategies covered include combinations of chemotherapy with checkpoint inhibitors, cytokines with adjuvants, and gene therapies with conventional drugs. RESULTS: Nanocarrier-based co-delivery enables synergistic therapy by simultaneously targeting tumor cells and the immune microenvironment. The co-delivery of chemotherapeutics with immune checkpoint inhibitors promotes antigen expression by relieving immune suppression within the tumor microenvironment, hence improving the subsequent immune activation while increasing the infiltration of T-cells. Similarly, nanoparticle delivery of immunostimulatory cytokines produces local immune activation with reduced systemic toxicity, and gene-editing nanotherapies have also emerged. CONCLUSION: Nanotechnology-assisted co-delivery strategies overcome the immunotherapy limitations in ovarian cancer. Preclinical and early clinical outcomes are encouraging, with some challenges in safety, synthesis, and regulatory concerns. Continued innovation in biodegradable nanocarriers and rigorous clinical evaluation are crucial to fully realize the clinical impact in ovarian cancer.
Inhibitory Effect of .-Derived Extracellular Vesicles Loaded with Celecoxib on Osteoclast Differentiation in Periodontitis.
Gao H, Yin S, Yan Y … +10 more , Jin Y, Jiang M, Liu Y, Lu L, Ge Z, Cai Y, Wang H, Li C, Pan Y, Lin L
Int J Nanomedicine · 2026 · PMID 42052514 · Full text
PURPOSE: Alveolar bone resorption in periodontitis is the primary clinical cause of tooth loss. This study aimed to investigate the inhibitory effect of .-derived extracellular vesicles (AC-EVs) loaded with celecoxib (AC...
PURPOSE: Alveolar bone resorption in periodontitis is the primary clinical cause of tooth loss. This study aimed to investigate the inhibitory effect of .-derived extracellular vesicles (AC-EVs) loaded with celecoxib (ACEV@CEL) on alveolar bone resorption. METHODS: AC-EVs were isolated using gradient centrifugation in combination with ultracentrifugation, after which celecoxib was incorporated via ultrasonication to generate ACEV@CEL. Subsequently, a rat periodontitis model was established, and local administration was performed to systematically evaluate the biocompatibility and therapeutic effects on alveolar bone resorption. In vitro, after determining the optimal administration dose for each treatment group, we confirmed that RAW264.7 cells were able to internalize AC-EVs and ACEV@CEL. In the established in vitro periodontitis model, ACEV@CEL significantly inhibited osteoclast differentiation, and this inhibitory effect was stronger than that of either AC-EVs or celecoxib alone. RESULTS: In vivo, ACEV@CEL exhibited good biocompatibility and effectively suppressed alveolar bone resorption in rats with periodontitis. In vitro, ACEV@CEL was internalized by RAW264.7 cells and inhibited their differentiation into osteoclasts. CONCLUSION: ACEV@CEL is able to suppress osteoclast differentiation under periodontitis conditions, while demonstrating favorable biocompatibility and safety, suggesting its potential as a therapeutic agent for periodontitis and warranting further long-term investigation.
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