International Journal Of Nanomedicine[JOURNAL]
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200 papers
The Emerging Role of Nanocarrier-Based Delivery Systems for cGAS-STING Activation in Cancer Immunotherapy.
Zhu G, Li D, Zhang H … +5 more , Wang J, Li X, Zeng L, Zhang L, Yu L
Int J Nanomedicine · 2026 · PMID 42267310 · Full text
Activation of the cGAS-STING pathway is a potential strategy to potentiate anti-tumor immunity. However, clinical translation of STING agonists such as cGAMP is hampered by poor targeting, enzymatic degradation, and syst...
Activation of the cGAS-STING pathway is a potential strategy to potentiate anti-tumor immunity. However, clinical translation of STING agonists such as cGAMP is hampered by poor targeting, enzymatic degradation, and systemic off-target toxicity. Nanocarrier-based drug delivery systems (nano-DDS) overcome these limitations by improving stability, bioavailability, and tumor-specific delivery. This review summarizes recent advances in lipid-based, polymeric, metallic, mesoporous silica, and exosomal for STING agonist delivery. These nanoplatforms enable precise drug delivery and controlled release, thereby significantly augmenting anti-tumor immune responses. We further discuss combination strategies of STING nanoagonists with radiotherapy, chemotherapy, phototherapy, and immune checkpoint inhibitors. Finally, we outline current challenges and future directions, including protein corona effects, scalable manufacturing, and personalized therapy.
Bone Marrow-Derived Macrophages Loaded with Boron Carbide Nanoparticles Targeting the Glioblastoma Microenvironment for Boron Neutron Capture Therapy.
Rudawska A, Szczygieł A, Węgierek-Ciura K … +9 more , Mierzejewska J, Kozień D, Żeliszewska P, Chaszczewska-Markowska M, Rusiniak P, Wątor K, Pędzich Z, Pajtasz-Piasecka E, Szermer-Olearnik B
Int J Nanomedicine · 2026 · PMID 42261359 · Full text
INTRODUCTION: Boron neutron capture therapy (BNCT) is a targeted radiotherapy that represents a promising treatment for glioblastoma multiforme. BNCT efficacy depends on selective boron carriers capable of crossing the b...
INTRODUCTION: Boron neutron capture therapy (BNCT) is a targeted radiotherapy that represents a promising treatment for glioblastoma multiforme. BNCT efficacy depends on selective boron carriers capable of crossing the blood-brain barrier (BBB). Therefore, we propose an original strategy for boron delivery in BNCT, based on the cellular carriers. This study assessed the ability of bone marrow-derived macrophages (BMDMs) to accumulate boron carbide (BC) nanoparticles, transport them across an in vitro BBB model toward glioblastoma cell-conditioned medium, and interact with tumor cells. METHODS: The uptake and accumulation of BC nanoparticles by BMDMs in different polarization states (M0, M1, M2) were confirmed by holotomography and ICP-MS. The scratch assay assessed spontaneous migration of BMDMs loaded with BC nanoparticles. The Transwell system was used to determine the ability of BMDMs with BC to cross bEnd.3 brain endothelial cell monolayer, mimicking the BBB, toward GL-261 glioblastoma cell-conditioned medium rich in CCL2. Macrophage interactions with glioblastoma spheroids were investigated using the CellTiter-Glo 3D Cell Viability Assay and flow cytometry. RESULTS: All BMDM populations demonstrated the ability to accumulate BC nanoparticles, with the significantly highest boron concentration detected in M1 macrophages (21.53 ± 1.64 mg/L per 10 cells). Moreover, M0, M1, and M2 macrophages loaded with BC nanoparticles were capable of migrating through the brain endothelial cell monolayer, toward the glioblastoma cell-conditioned medium. BMDMs with nanoparticles did not affect the viability of glioblastoma spheroids after 6 days of co-culture, in contrast to macrophages without nanoparticles, which increased the survival of tumor cells. Importantly, CD206 expression was not increased in M1 macrophages after contact with spheroids, and was lower in M2 macrophages loaded with BC nanoparticles compared to control M2 macrophages. CONCLUSION: BMDMs are promising carriers of BC nanoparticles for BNCT due to their ability to cross the in vitro BBB model toward the glioblastoma microenvironment.
Royal Jelly-Derived Extracellular Vesicles: Key Bioactive Components Mediating Anti-Hepatocellular Carcinoma Activity.
Chi X, Jia L, Wang Y … +5 more , Liu C, Wang S, Liu Z, Zhang G, Xu B
Int J Nanomedicine · 2026 · PMID 42261358 · Full text
PURPOSE: To investigate the role of royal jelly derived extracellular vesicles (RJEVs) as key active components contributing to the anti-hepatocellular carcinoma (HCC) effects of royal jelly and to elucidate the underlyi...
PURPOSE: To investigate the role of royal jelly derived extracellular vesicles (RJEVs) as key active components contributing to the anti-hepatocellular carcinoma (HCC) effects of royal jelly and to elucidate the underlying mechanisms. PATIENTS AND METHODS: This study used H22 tumor-bearing mice as an in vivo model. RJEVs were isolated and identified and their effects were evaluated after oral administration. Analyses included the assessment of liver-targeting properties, immune and antioxidant responses, gut microbiota composition (specifically Muribaculaceae abundance), and short-chain fatty acid metabolism. This study also examined the influence of RJEVs on translation-related signaling networks and the Phosphatidylinositol 3-kinase (PI3K) / Protein Kinase B (AKT) signaling pathway to determine their role in promoting tumor cell apoptosis. RESULTS: Orally administered RJEVs exhibited liver-accumulating properties in H22 tumor-bearing mice and demonstrated moderate antitumor efficacy. They enhanced immune and antioxidant responses, increased the abundance of Muribaculaceae, modulated gut microbiota composition, and improved short-chain fatty acid metabolism. Mechanistically, RJEVs synergistically regulate translation-related signaling networks and remodel the immune microenvironment, ultimately promoting tumor cell apoptosis via the PI3K/AKT signaling pathway. CONCLUSION: These findings provide novel insights into the functional role of royal jelly by identifying RJEVs as important bioactive constituents that contribute to the anti-HCC effects by modulating the immune microenvironment, gut microbiota, and PI3K/AKT signaling. This offers both theoretical and methodological advances in research on the bioactive components of bee products.
-Derived Extracellular Vesicles Ameliorate Alcohol-Exacerbated Experimental Autoimmune Prostatitis by Inhibiting M1 Macrophage Polarization.
Zhu Q, Liu Y, Hu W … +7 more , Liu Y, Fu S, Xie W, Liu J, Xiong Y, Sun T, Gong B
Int J Nanomedicine · 2026 · PMID 42261357 · Full text
PURPOSE: This study investigated how alcohol exacerbated chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and assessed gut microbiota-targeted therapeutic strategies. METHODS: An alcohol‑treated experimental au...
PURPOSE: This study investigated how alcohol exacerbated chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and assessed gut microbiota-targeted therapeutic strategies. METHODS: An alcohol‑treated experimental autoimmune prostatitis (EAP) mouse model was established to evaluate the exacerbating effect of alcohol on CP/CPPS. The involvement of gut microbiota was assessed by antibiotic depletion and fecal microbiota transplantation (FMT). 16S rRNA sequencing was applied to profile microbial alterations, particularly the abundance of (). Oral administration of live or intravenous injection of -derived extracellular vesicles (LjEVs) was tested as therapeutic interventions. Mechanistic studies were conducted in lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophages using transcriptomics, qRT-PCR, Western blot, and flow cytometry. RESULTS: Alcohol consumption aggravated pelvic tactile hypersensitivity and prostatic inflammation, increased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and promoted M1 macrophage polarization in EAP mice. Fecal microbiota transplantation from alcohol-fed EAP mice reproduced the aggravated phenotype, confirming that gut microbiota mediates this effect. Alcohol specifically reduced the relative abundance of . Oral or intravenous LjEVs alleviated tactile hypersensitivity and inflammation, and inhibited M1 macrophage polarization in alcohol-fed EAP mice. In vitro, LjEVs were internalized by macrophages, suppressed LPS-induced M1 macrophage polarization and pro-inflammatory gene expression, and inhibited TNF-α/NF-κB signaling. Exogenous TNF-α reversed the inhibitory effects of LjEVs on M1 macrophage polarization. CONCLUSION: Alcohol exacerbated EAP by reducing , which in turn promoted prostatic M1 macrophage polarization via the TNF-α/NF-κB pathway. Supplementation with or LjEVs ameliorated the disease by suppressing this pathway, offering a microbiota-targeted therapy for alcohol-aggravated CP/CPPS.
Bridging Preclinical and Clinical Gaps in Ocular Therapeutics: Hydrogel Drug Delivery and 3D Tissue Models.
Barar J, Aliakbari A, Omidi Y
Int J Nanomedicine · 2026 · PMID 42261356 · Full text
Affecting over 2.2 billion people globally, ocular diseases represent a profound public health challenge, with vision loss projected to increase by 55% by 2050. Ocular drug delivery is fundamentally constrained by the ey...
Affecting over 2.2 billion people globally, ocular diseases represent a profound public health challenge, with vision loss projected to increase by 55% by 2050. Ocular drug delivery is fundamentally constrained by the eye's anatomical and physiological barriers, limiting bioavailability and necessitating repeated invasive administration. Hydrogel-based drug delivery systems (DDSs) have emerged as transformative platforms offering controlled drug release, mucoadhesive precorneal retention, and stimulus-responsive phase transitions for anterior and posterior segment diseases. Formulated from natural biopolymers (e.g., hyaluronic acid, chitosan, gelatin, and alginate) and synthetic platforms (e.g., thermosensitive poloxamers, pH-responsive carbomers, and photo-crosslinked polyethylene glycol systems), these networks sustain therapeutic concentrations while reducing the burden of invasive procedures. Despite these advances, clinical translation remains critically impeded by the limited predictive capacity of conventional two-dimensional cell cultures and animal models, which fail to replicate human ocular tissue architecture, barrier integrity, and disease pathophysiology. Three-dimensional (3D) ocular organoids (e.g., corneal epithelial, lens, lacrimal gland, and retinal constructs derived from patient-specific induced pluripotent stem cells) alongside eye-on-a-chip microfluidic platforms provide human-relevant microphysiological systems for evaluating hydrogel performance, drug transport, efficacy, and biocompatibility under normal conditions. Critically, the integration of hydrogel-based DDSs with advanced 3D tissue models offers a transformative strategy to bridge the persistent preclinical-to-clinical translation gap in ocular therapeutics. Herein, we critically appraise the current landscape of hydrogel-based ocular DDSs and their integration with 3D organoid and organ-on-chip platforms, identifying key opportunities and barriers along the translational pathway toward next-generation therapeutics for vision-threatening ocular diseases.
Environmental Micro-Nanoplastics and Musculoskeletal Disorders: Current Research and Insights.
Ju C, Dong H, Liu R … +3 more , Ma Y, Luo R, Hu H
Int J Nanomedicine · 2026 · PMID 42256670 · Full text
In recent years, micro-nanoplastics, as globally prevalent emerging environmental pollutants, can enter the human body through oral ingestion, respiratory inhalation, and dermal contact, and widely distribute in diverse...
In recent years, micro-nanoplastics, as globally prevalent emerging environmental pollutants, can enter the human body through oral ingestion, respiratory inhalation, and dermal contact, and widely distribute in diverse tissues including blood, placenta, lung, bone marrow, and bone, thereby arousing widespread concern regarding their health risks. As an essential functional system of the human body, the skeletal system is involved in mechanical support, metabolic homeostasis, and immune regulation. Disruption of skeletal homeostasis may induce a series of musculoskeletal diseases, such as osteoporosis, rheumatoid arthritis, intervertebral disc degeneration, and osteoarthritis. Accumulating evidence has verified that micro-nanoplastics can accumulate in human bone, cartilage, intervertebral disc, and bone marrow, and destroy skeletal homeostasis via multiple mechanisms, including inflammatory response, oxidative stress, pyroptosis, ferroptosis, cellular senescence, and epigenetic regulation, thus participating in the occurrence and development of musculoskeletal diseases. This paper systematically reviews the sources, classification, environmental distribution, human exposure pathways, and systemic toxic effects of micro-nanoplastics. It emphatically expounds the impacts and potential molecular mechanisms of micro-nanoplastics on osteoporosis, intervertebral disc degeneration, rheumatoid arthritis, osteoarthritis, lupus-related musculoskeletal lesions, and osteosarcoma progression. Furthermore, we summarize the detection methods and research limitations of micro-nanoplastics in skeletal tissues, and prospect future directions in environmental prevention and control, clinical translation, and high-risk population monitoring. This review is expected to provide novel ideas for mechanistic investigation, risk assessment, and clinical translation of micro-nanoplastic-associated skeletal diseases.
Diabetes-Related Metabolic Osteoarthritis: Advanced Glycation-Collagen Axis, Cartilage Stiffening, and Biomaterials-Based Therapeutic Strategies.
Li J, Cao B, Yu S … +7 more , Li C, Xue M, Xie Q, Luo C, Duan C, Li Z, Jin C
Int J Nanomedicine · 2026 · PMID 42239648 · Full text
Diabetes mellitus, particularly type 2 diabetes, has been associated in some studies with increased osteoarthritis (OA) risk, greater symptom burden, and structural progression; however, epidemiological evidence remains...
Diabetes mellitus, particularly type 2 diabetes, has been associated in some studies with increased osteoarthritis (OA) risk, greater symptom burden, and structural progression; however, epidemiological evidence remains heterogeneous, and the extent to which diabetes independently contributes to OA after accounting for obesity, adiposity, physical inactivity, and other metabolic confounders remains debated. In metabolically susceptible patients, chronic hyperglycemia, insulin resistance, carbonyl stress, and low-grade inflammation may contribute to disruption of the joint microenvironment. One proposed mechanism involves the accumulation of advanced glycation end products (AGEs), which can cross-link with type I/II collagen and may increase extracellular matrix crosslinking and stiffness. Through these biochemical and biomechanical effects, the AGE-collagen axis may influence chondrocyte mechanotransduction, inflammatory signaling, matrix turnover, and cell survival, thereby providing a plausible but not yet fully validated link between systemic metabolic dysfunction and OA-relevant structural degeneration. Recent advances in biomaterials may offer experimental and translational strategies to modulate the glycated, inflamed, and mechanically altered joint microenvironment. These approaches include stiffness-tunable and stimuli-responsive hydrogels, nanocarriers designed to deliver anti-AGE agents or AGE-cleaving enzymes, osteochondral gradient scaffolds that mimic native tissue transitions, and immunomodulatory materials that may attenuate local inflammation. At present, these interventions should be viewed primarily as preclinical or early translational strategies rather than established disease-modifying therapies. This review discusses the potential molecular and biomechanical implications of the AGE-collagen axis in diabetes-related OA, critically evaluates emerging biomaterials-based therapeutic approaches, and highlights preclinical evaluation models and outcome measures. Finally, we outline key translational challenges-including targeted delivery, long-term safety of degradation products, metabolic heterogeneity, patient stratification, and integration with systemic therapies-and propose methodological frameworks to support the future development of clinically testable biomaterials interventions.
ROS-pH Dual-Responsive Polydopamine Nanoparticles for Targeted Fasudil Delivery Ameliorate Multiple Pathologies in Diabetic Retinopathy.
Li J, Zhong Z, Tan Y … +8 more , Ma X, Wang R, Gao G, Zhang X, Zhou Z, Zhao Y, Liu J, Sun X
Int J Nanomedicine · 2026 · PMID 42232487 · Full text
BACKGROUND: The multifaceted pathogenesis of diabetic retinopathy (DR) involves numerous pathways, among which oxidative stress and Rho-associated kinase (ROCK) signaling are critically implicated. The failure of current...
BACKGROUND: The multifaceted pathogenesis of diabetic retinopathy (DR) involves numerous pathways, among which oxidative stress and Rho-associated kinase (ROCK) signaling are critically implicated. The failure of current anti-VEGF monotherapies to address these key pathological processes limits their efficacy. While the ROCK inhibitor Fasudil is a promising candidate, its clinical translation for DR is hindered by poor ocular retention and lack of target specificity. METHODS: We engineered a reactive oxygen species (ROS)- and pH-dual responsive polydopamine nanoplatform (Fasudil@PDA) to deliver Fasudil while concurrently scavenging oxidative stressors. RESULTS: The Fasudil@PDA nanoparticles achieved a high drug loading capacity of ~28%. The release kinetics were specifically engineered to be responsive to the DR microenvironment. Under high ROS conditions in vitro, the platform demonstrated a sustained and efficient release profile, achieving a cumulative release of 87.3% over 56 days - demonstrating remarkable longevity. Separately, the pH-responsive drug release capability was also confirmed under acidic conditions. The platform effectively neutralized multiple ROS species in vitro and significantly restored endothelial barrier integrity by inhibiting the ROCK/MLC pathway. In a laser-induced choroidal neovascularization model, a single injection suppressed pathological angiogenesis by 45%. In diabetic mice, the same treatment markedly reduced vascular leakage, attenuated neuroinflammation, and restored retinal function, with b-wave amplitudes recovering to near-normal levels. CONCLUSION: This study establishes a multi-faceted nanotherapeutic strategy that synergizes sustained, long-acting ROCK inhibition with innate antioxidant activity. Designed to be activated by the pathological cues of DR, including acidic pH and ROS, our approach precisely targets multiple pathological pathways, offering a promising and translatable paradigm for overcoming the limitations of current monotherapies.
Apo-Transferrin Modified Natamycin-Loaded Liposomes Improve the Prognosis of Fungal Keratitis via Enhanced Antifungal and Anti-Inflammatory Activities.
Hu L, Luan J, Liu X … +5 more , Zhang Z, Tong Z, Qu Y, Jiang Z, Lin J
Int J Nanomedicine · 2026 · PMID 42232486 · Full text
BACKGROUND: The proliferation and establishment of infections by pathogenic microorganisms require essential nutrients, such as host-derived iron. The sequestration of iron by the host represents an ancient defense mecha...
BACKGROUND: The proliferation and establishment of infections by pathogenic microorganisms require essential nutrients, such as host-derived iron. The sequestration of iron by the host represents an ancient defense mechanism against microbial invasion. Apo-Transferrin (Apo-Tf) is a promising and novel antimicrobial agent with intrinsic iron sequestration properties and therefore merits clinical investigation. Given the characteristics of natamycin (NAT) such as its low aqueous solubility and significant ocular irritation, we developed apo-Tf decorated liposomes encapsulating NAT for the treatment of fungal keratitis (FK). METHODS: NAT was encapsulated into liposomes using the lipid film hydration method. Natamycin-loaded transferrin-conjugated liposomes (NAT@TF-LP) were synthesized via the post-insertion technique and characterized through zeta-sizer analysis, morphology and Fourier transform infrared (FTIR) spectroscopy. The encapsulation efficiency, loading capacity, and in vitro release profile were determined by ultraviolet spectrophotometry. The cytotoxicity, ocular surface irritation, and systemic safety of liposomal formulations were evaluated in corneal epithelial cells and mice. In vitro studies investigated the antifungal properties of NAT@TF-LP, while in vivo experiments assessed eye surface retention and therapeutic efficacy in an FK mouse model. RESULTS: The prepared liposomes exhibited a well-defined nanostructure with uniform dimensions and apo-Tf was effectively conjugated to the surface, as verified by the emergence of characteristic amide bands in FTIR analysis. The loading efficiencies of NAT@LP and NAT@TF-LP were 5.6% and 3.53% respectively, with encapsulation efficiencies above 96%. Both formulations facilitated sustained NAT release and prolonged ocular surface retention. The in vitro release of NAT from NAT@TF-LPs followed a diffusion-controlled profile, exhibiting an excellent fit to both Higuchi and Korsmeyer-Peppas models. Additionally, they exhibited good biosafety profiles in both cytotoxicity and ocular irritation assays. In vivo, NAT@TF-LPs demonstrated superior therapeutic efficacy, resulting in a 15.4-fold reduction in corneal fungal burden (approximately 1.19-log reduction) compared to the free NAT group, alongside a marked decrease in the protein expression of pro-inflammatory cytokines, including IL-1β (65.0%), IL-6 (59.0%), and TNF-α (73.0%), with a 69.3% enhancement in anti-inflammatory IL-10 levels. CONCLUSION: The apo-Tf functionalized liposomal system improves NAT ocular bioavailability and exhibits augmented antifungal and therapeutic efficacies. This enhancement is attributed to the combined benefits of the liposomal platform and the inherent antimicrobial properties of apo-Tf. This study highlights the promising potential of NAT@TF-LPs for the pharmacotherapy of FK.
A Porphyrinic Covalent Organic Polymer Nanoplatform for Carborane Delivery and Multifunctional Imaging-Guided Boron Neutron Capture Therapy of Breast Cancer.
Ren J, Wang T, Zuo C … +2 more , Zhang R, Li L
Int J Nanomedicine · 2026 · PMID 42226971 · Full text
INTRODUCTION: The advancement of boron neutron capture therapy (BNCT) is critically dependent on the development of efficient and traceable boron delivery agents. METHODS: We designed and synthesized a porphyrin-based co...
INTRODUCTION: The advancement of boron neutron capture therapy (BNCT) is critically dependent on the development of efficient and traceable boron delivery agents. METHODS: We designed and synthesized a porphyrin-based covalent organic polymer (T-COP) loaded with ortho-carborane (o-CB) and surface-functionalized with DSPE-PEG, successfully constructing a novel nanoplatform (T-COP@o-CB NPs). This platform enables real-time imaging-guided boron neutron capture therapy (BNCT), providing a new strategy for the treatment of breast cancer. RESULTS: The resulting nanocomposite exhibits a high boron content (28.82 wt%), excellent colloidal stability, and pronounced fluorescence derived from the porphyrin building blocks, thereby enabling real-time tracking. In vitro, T-COP@o-CB NPs have outstanding biocompatibility, efficient cellular uptake, and prolonged intracellular retention in 4T1 breast cancer cells. In vivo fluorescence imaging confirms effective tumor localization and retention following intratumoral injection. Most notably, in a subcutaneous breast cancer mouse model, the T-COP@o-CB NPs with thermal neutron irradiation achieve 73.04% tumor inhibition compared to all control groups, while exhibiting no significant systemic toxicity as validated by body weight monitoring and histopathological analysis. CONCLUSION: This work presents a promising theranostic platform that combines high boron loading, inherent self-imaging capability, and effective tumor inhibition, offering a new strategy for precise and enhanced BNCT.
Nanocarrier-Enabled Melittin Therapy: Mechanistic Advances, Therapeutic Applications, and Translational Challenges.
Xiong Y, Cai H, Jia S … +4 more , Gong B, Hou K, Wu H, Chen H
Int J Nanomedicine · 2026 · PMID 42226970 · Full text
Melittin, a 26-amino-acid amphipathic peptide derived from bee venom, has attracted sustained interest in nanomedicine because of its broad anticancer, antiviral, and anti-inflammatory activities. These effects arise not...
Melittin, a 26-amino-acid amphipathic peptide derived from bee venom, has attracted sustained interest in nanomedicine because of its broad anticancer, antiviral, and anti-inflammatory activities. These effects arise not only from direct membrane disruption, but also from secondary intracellular stress signaling and context-dependent immunomodulatory responses. The same mechanism, however, also underlies melittin's major limitation: potent biological activity is closely coupled to hemolysis, nonspecific cytotoxicity, and poor systemic tolerability. For this reason, the central question in melittin nanomedicine is no longer whether the peptide is bioactive, but how that activity can be spatially, temporally, and pharmacologically constrained in vivo. Nanocarrier engineering has therefore become integral to melittin development, with lipidic, polymeric, inorganic, and hybrid systems being explored to reduce premature toxicity, improve lesion-site accumulation, regulate peptide release, and enable active or stimulus-responsive targeting. In this review, we synthesize current progress from three linked perspectives: the mechanistic basis of melittin action, the disease-specific logic of its reported applications, and the translational criteria that distinguish proof-of-concept platforms from development-relevant ones. This review was prepared by searching peer-reviewed literature published primarily between 2020 and early 2026 in PubMed, Web of Science, and Scopus, with priority given to studies addressing melittin biological activity, nanocarrier formulation design, toxicity modulation, and translational considerations. Across the current literature, the most decisive issues are not efficacy alone, but the extent to which toxicity attenuation, exposure control, PK/PD interpretability, and formulation tractability can be achieved within the same platform. The available evidence suggests that melittin is most plausibly advanced in delivery-controlled settings, particularly localized, route-constrained, or selected combination-oriented applications, whereas broader systemic use still requires stronger evidence in long-term safety, pharmacological standardization, and product-level reproducibility.
Nanozymes for Bone Regeneration: Mechanistic Insights into Immune and Metabolic Microenvironment Modulation.
Wang Y, Song M, Chen S … +7 more , He Y, Chen S, Li Z, Xu M, Zhang Q, Rui Y, Shen J
Int J Nanomedicine · 2026 · PMID 42226969 · Full text
Nanozymes, a class of nanomaterials with intrinsic enzyme-mimetic properties, have emerged as promising therapeutic platforms for bone regeneration due to their low cost, high stability, and multifunctionality. This revi...
Nanozymes, a class of nanomaterials with intrinsic enzyme-mimetic properties, have emerged as promising therapeutic platforms for bone regeneration due to their low cost, high stability, and multifunctionality. This review provides mechanistic insights and translational perspectives on how nanozymes act as microenvironmental "remodelers" to enhance bone repair. Representative systems-including cerium oxide (CeO), manganese-based (MnO/MnO), and Prussian blue (PBNPs)-exert therapeutic effects by scavenging ROS, promoting M2 macrophage polarization, restoring mitochondrial function, suppressing the NLRP3/NF-κB signaling axis, and clearing deleterious metabolites such as lactate. We systematically discuss immune regulation, metabolic intervention, and their synergistic crosstalk, highlighting their capacity for spatiotemporal coordination of angiogenesis and antimicrobial defense. Finally, we outline future directions, including enhancing catalytic specificity, improving in vivo stability, addressing biosafety and pharmacokinetics, developing intelligent nanozyme designs, and establishing clinically relevant evaluation models to accelerate translation into effective bone therapies.
The Role and Mechanism of Nanozymes in Burn Wound Healing.
Zou L, Zhang M, Lin L … +2 more , Zhou Y, Shen C
Int J Nanomedicine · 2026 · PMID 42226968 · Full text
The treatment of burn wounds is a complex and lengthy process, including infection control, inflammation modulation, tissue regeneration, and scar management. Although significant progress has been achieved, numerous cli...
The treatment of burn wounds is a complex and lengthy process, including infection control, inflammation modulation, tissue regeneration, and scar management. Although significant progress has been achieved, numerous clinical challenges persist, especially the increased bacterial resistance, the risk of wound sepsis, and the issue of serious hypertrophic scar. In recent years, nanozymes have emerged as a hotspot in materials research and increasingly been applied to promote burn wound healing. Possessing multiple enzyme-like activities, nanozymes can integrate antibacterial, anti-inflammatory, and pro-angiogenic effects, among others. Meanwhile, nanozymes offer advantages such as less prone to inducing drug resistance, high stability, and simple preparation, which indicate broad application prospects compared with antibiotics, natural enzymes, and traditional nanomaterials. This review provides a comprehensive overview of the pathophysiology involved in burn wounds and introduces nanozymes exhibiting a variety of enzyme-like activities including oxidase (OXD), peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), haloperoxidase (HPO), nitrite reductase (NiRs), and hydrolase. The potential mechanisms by which nanozymes promote burn wound healing are summarized and elucidated from the aspects of anti-bacteria, anti-oxidative stress, anti-inflammation, pro-angiogenesis, and anti-scarring. Finally, we discuss the limitations of the current study and offer an outlook for future research, hoping to pave the way for the next generation nanozymes in the treatment of burn wounds.
A Thermosensitive Hydrogel Embedded with Metronidazole-Derived Carbon Dots for Antibacterial Treatment of Periodontitis.
Wang D, Feng X, Tang X … +3 more , Hu Y, Xing X, Xiao Y
Int J Nanomedicine · 2026 · PMID 42226967 · Full text
INTRODUCTION: Microorganisms are the primary initiators of periodontitis, and local antibiotic therapy remains an important adjunctive strategy for controlling periodontal pathogenic bacteria. However, conventional antim...
INTRODUCTION: Microorganisms are the primary initiators of periodontitis, and local antibiotic therapy remains an important adjunctive strategy for controlling periodontal pathogenic bacteria. However, conventional antimicrobial agents often exhibit limited local retention and may induce cytotoxicity or bacterial resistance. This study aimed to develop a thermosensitive hydrogel system incorporating metronidazole-derived carbon dots (Met-CDs) for localized antibacterial treatment of periodontitis. METHODS: Met-CDs were synthesized via a one-step hydrothermal method at different temperatures, and their physicochemical characteristics were compared. Human gingival fibroblasts (HGFs) were used to evaluate cytocompatibility through CCK-8 and live/dead staining assays. Antibacterial activity of Met-CDs against Streptococcus sanguinis, Porphyromonas gingivalis, and Fusobacterium nucleatum was assessed using metabolic activity assays, live/dead bacterial staining, scanning electron microscopy, and Western blot analysis. A Poloxamer 407 (P407)-based thermosensitive hydrogel was further fabricated and characterized by rheological, swelling, and in vitro release analyses, while its antibacterial activity was evaluated using agar well antibacterial assays. In vivo biosafety was evaluated in an SD rat model through hematological analysis, inflammatory cytokine ELISA, and histological staining, while therapeutic efficacy was assessed by bacterial load analysis, immunohistochemical analysis, and micro-CT assessment. RESULTS: Met-CDs synthesized at 180 °C retained relatively enriched polar and oxidized surface groups compared with those synthesized at 250 °C, which was associated with enhanced antibacterial activity, and were therefore selected for subsequent studies. Compared with metronidazole (Met), Met-CDs demonstrated enhanced antibacterial activity and lower cytotoxicity toward HGFs. Western blot analysis suggested that the antibacterial effect of Met-CDs may be associated with bacterial membrane disruption. The Met-CDs@P407 hydrogel exhibited favorable thermosensitive behavior, swelling properties, in vitro release characteristics, and retained in vitro antibacterial activity. In vivo experiments demonstrated acceptable biosafety of the hydrogel system, with no obvious systemic inflammatory response or organ toxicity observed under the tested conditions. In addition, the hydrogel reduced periodontal bacterial burden and alleviated alveolar bone resorption in SD rats with experimental periodontitis. Although immunohistochemical staining revealed no obvious enhancement of VEGF expression, indicating a limited effect on VEGF-mediated angiogenic activity, decreased TNF-α expression was observed in periodontal tissues, suggesting that Met-CDs@P407 may alleviate local inflammatory responses through effective control of periodontal pathogenic bacteria. CONCLUSION: The Met-CDs@P407 thermosensitive hydrogel demonstrated favorable antibacterial activity, cytocompatibility, localized retention potential, and in vivo therapeutic efficacy, suggesting its potential as a localized antimicrobial biomaterial for periodontitis treatment.
HACC-TNF-α-VLP Nanoparticles Facilitate HSP90-Dependent Antigen Cross-Presentation to Enhance CD8⁺ T Cell and Mucosal Immunity Against Foot-and-Mouth Disease.
Lv L, Su Y, Chen S … +6 more , Su W, Yin Y, Ning P, Liu S, Yuan W, Li L
Int J Nanomedicine · 2026 · PMID 42226966 · Full text
OBJECTIVE: Current foot-and-mouth disease (FMD) vaccines lack the efficient induction of CD8 T cell-mediated cellular immunity and mucosal protection, highlighting the need for novel immunomodulatory delivery systems. ME...
OBJECTIVE: Current foot-and-mouth disease (FMD) vaccines lack the efficient induction of CD8 T cell-mediated cellular immunity and mucosal protection, highlighting the need for novel immunomodulatory delivery systems. METHODS: HACC-TNF-α-virus-like particles (VLPs) nanoparticles were prepared via the ionic cross-linking method, followed by systematic evaluation of morphological characteristics, particle size distribution, in vitro release behavior, stability, and biotoxicity. In vitro experiments, the prepared nanoparticles were co-cultured with bone marrow-derived dendritic cells (BMDCs), and flow cytometry (FCM) and cytokine array assays were subsequently used to detect the activation status of dendritic cells. The combined application of laser confocal microscopy and FCM was employed to further explore the antigen cross-presentation ability mediated by the nanoparticles. For the in vivo experiments, mice were administered with the nanoparticles via two routes: intranasal immunization and subcutaneous immunization. The levels of specific antibodies in the serum were quantitatively detected using enzyme-linked immunosorbent assay, and lymphocyte proliferation assay, immunohistochemical technology, and FCM were combined to comprehensively evaluate the intensity of CD8 T cell immune response and mucosal immune effects in mice. RESULTS: HACC-TNF-α-VLPs nanoparticles were successfully prepared, showing spherical morphology (~162.7 nm, -11.9 mV zeta potential), 84.40% encapsulation efficiency, 12.82% drug loading, and sustained release (75.83% cumulative release on day 4). They were non-cytotoxic to L929 cells at concentrations of ≤400 μg/mL. HACC-TNF-α-VLPs nanoparticles promoted BMDCs maturation, facilitated BMDCs endocytosis of FMDV-VLPs, and antigen cross-presentation mediated by heat shock protein 90. Moreover, it can activate CD8 T cells in vitro via cross-presentation. HACC-TNF-α-VLPs nanoparticles upregulated cytotoxic T cells, tissue-resident memory T cells, sIgA, and systemic FMDV-specific antibodies in vivo. CONCLUSION: HACC-TNF-α-VLPs nanoparticles exhibit potent immunomodulatory activity by efficiently mediating antigen cross-presentation and play a dual role in both induction of CD8 T cell responses and mucosal immunity, indicating their potential role in FMD novel vaccine development.
CD71-Targeted and ROS-Responsive Micelles for Homoharringtonine Delivery to Enhance Therapeutic Efficiency Against FLT3-ITD Acute Myeloid Leukemia.
Tang Y, Li J, Ye W … +5 more , Du Y, Zhang Y, Yang Y, Ye Y, Gong Y
Int J Nanomedicine · 2026 · PMID 42226965 · Full text
PURPOSE: The FMS-like tyrosine kinase 3- internal tandem duplication (FLT3-ITD) subtype of acute myeloid leukemia (AML) is associated with poor clinical outcomes. Homoharringtonine (HHT), a natural protein inhibitor, has...
PURPOSE: The FMS-like tyrosine kinase 3- internal tandem duplication (FLT3-ITD) subtype of acute myeloid leukemia (AML) is associated with poor clinical outcomes. Homoharringtonine (HHT), a natural protein inhibitor, has shown strong activity against FLT3-ITD AML. However, its clinical use is limited by rapid clearance and systemic toxicity. To address these limitations, a CD71-targeted, ROS-responsive micelle (TDTP/HHT) was developed for precise and efficient HHT delivery. METHODS: CD71 expression was assessed in AML patient samples and cell lines. TDTP/HHT was prepared by self-assembly using a D-peptide ligand (T7) for CD71 targeting and a ROS-cleavable linker for stimuli-responsive drug release. Cellular uptake, cytotoxicity and signaling pathway inhibition were evaluated in vitro across AML cell lines with distinct FLT3 statuses. The therapeutic efficacy of TDTP/HHT was further validated in a disseminated AML xenograft mouse model. RESULTS: Cytotoxicity analysis revealed that FLT3-ITD AML is intrinsically sensitive to HHT. Analysis of patient samples and cell lines revealed high CD71 expression and elevated ROS levels in AML, most predominantly in the FLT3-ITD subtype. The designed TDTP/HHT showed prolonged circulation time, ROS-responsive drug release, and stable targeting capacity. It did not compete with endogenous transferrin for binding sites but instead demonstrated transferrin-promoted cellular uptake. Both in vitro and in vivo studies confirmed that TDTP/HHT significantly inhibited the growth of FLT3-ITD AML cells. Mechanistically, TDTP/HHT suppressed multiple key downstream signaling proteins of FLT3-ITD. In addition, the system also remained active in CD71-high FLT3-WT AML cells, although higher HHT concentrations were required. CONCLUSION: This study presents a novel targeted nanodrug that exploits the intrinsic HHT sensitivity of FLT3-ITD AML cells and their characteristic high CD71 expression and elevated ROS levels. Therefore, this platform is particularly suited for the treatment of FLT3-ITD AML while potentially applicable to other AML subtypes with high CD71 expression. By enabling specific intracellular accumulation of HHT and multitarget inhibition of FLT3 signaling pathways, this system achieves enhanced anti-AML efficacy both in vitro and in vivo, offering strong potential for future clinical translation.
Plant-Derived Extracellular Vesicles for Nanomedicine in Cardiopulmonary Diseases: A Narrative Review.
Zhang JJ, Huang YQ, Liu X … +1 more , Xie P
Int J Nanomedicine · 2026 · PMID 42226964 · Full text
This narrative review summarizes research progress on plant-derived extracellular vesicles (PEVs) for nanomedicine in cardiopulmonary system diseases, based on key literature covering isolation, engineering, and disease...
This narrative review summarizes research progress on plant-derived extracellular vesicles (PEVs) for nanomedicine in cardiopulmonary system diseases, based on key literature covering isolation, engineering, and disease mechanisms. PEVs possess high biocompatibility, low immunogenicity, broad source availability, and scalability. Their bioactive cargo (proteins, nucleic acids, lipids, secondary metabolites) regulates inflammation, oxidative stress, apoptosis, and fibrosis. This review systematically discusses PEV characteristics, large-scale isolation, and engineering approaches, with a focus on multi-target and cell-specific mechanisms in atherosclerosis, myocardial infarction, COPD, and pulmonary fibrosis. Although challenges in standardization, in vivo mechanisms, and translation remain, engineered PEVs hold promise as efficient and safe nanomedicines. The unique contribution of this review is to integrate PEV preparation and engineering with their disease-specific mechanisms, providing a coherent framework for future translational research in cardiopulmonary nanomedicine.
Prussian Blue Nanozyme Potentiates Venetoclax Efficacy in Acute Myeloid Leukemia by Inducing a More Mature Phenotype.
Yang F, Wu H, Yao J … +8 more , Peng X, Yang A, Wen T, Meng J, Liu J, Zhang Y, Wang T, Xu H
Int J Nanomedicine · 2026 · PMID 42226963 · Full text
INTRODUCTION: Acute Myeloid Leukemia (AML) is characterized by the clonal expansion of undifferentiated myeloid precursors and is associated with notably higher incidence and mortality rates in the elderly population. Wh...
INTRODUCTION: Acute Myeloid Leukemia (AML) is characterized by the clonal expansion of undifferentiated myeloid precursors and is associated with notably higher incidence and mortality rates in the elderly population. While the BCL-2 inhibitor Venetoclax has transformed the therapeutic landscape for patients with AML who were ineligible for intensive therapy, primary and acquired resistance remained major obstacles to durable responses. METHODS: In this study, an ultra-small Prussian Blue nanozyme (USPBNP)-based "maturation-priming" strategy was investigated to enhance Venetoclax sensitivity. USPBNPs were synthesized and characterized for physicochemical properties and enzyme-mimetic activities. Their differentiation-inducing effects were evaluated in Venetoclax-sensitive MOLM-13 cells, acquired-resistant RMOLM-13 cells, primary-resistant OCI-AML3 cells, murine C1498 AML cells, an AML1-ETO/KIT murine transplant model, and primary human AML bone marrow mononuclear cells. Cellular maturation was assessed by morphological analysis and flow-cytometric detection of lineage-associated markers. Venetoclax sensitization was evaluated by apoptosis assays, mitochondrial membrane potential analysis, and detection of apoptosis-related proteins. RESULTS: In vitro, USPBNPs effectively reshaped the leukemic phenotype, driving differentiation in MOLM-13, RMOLM-13, and OCI-AML3 AML cells, evidenced by the reduced nucleo-cytoplasmic ratio as well as up-regulated CD11b, CD14, CD235a and CD41a. The "maturation-priming" effects were also confirmed through cross-species models in C1498 murine AML cells and a refractory AML1-ETO/KIT murine transplant mice model in vivo and in human clinical specimen. This phenotypic maturation lowered the apoptotic threshold of Venetoclax, resulting in mitochondrial membrane potential collapse, Caspase-3 activation, and the down-regulation of the resistance-associated protein MCL-1. CONCLUSION: These findings supported USPBNPs as a maturation-priming approach in AML models with distinct genetic backgrounds and Venetoclax resistance patterns. The combination of USPBNPs and Venetoclax coupled differentiation induction with apoptosis and might provide a potential strategy for improving Venetoclax responsiveness in AML.
Nanoparticle Drug Delivery Systems: The Future Direction for the Treatment of Tumors.
Zhao Y, Nie X, Yan H … +6 more , Ren J, Zhao J, Tong L, Zhao L, Zhang G, Liu H
Int J Nanomedicine · 2026 · PMID 42226962 · Full text
An increasing number of people worldwide are dying from cancer, with metastasis being the main cause of cancer-related deaths, but most of the drugs used to treat these patients have systemic toxicity. Fortunately, with...
An increasing number of people worldwide are dying from cancer, with metastasis being the main cause of cancer-related deaths, but most of the drugs used to treat these patients have systemic toxicity. Fortunately, with the development and application of nanodrug delivery systems, a large amount of research has been conducted on inorganic nanocarriers represented by metal nanocarriers, as well as organic nanocarriers represented by liposomal nanoparticles and polymeric micelles, as delivery systems for antitumor substances. These nanocarriers can not only increase the solubility and stability of hydrophobic drugs and prolong their circulation time in the blood, but also enable the loaded drugs to have tumor-targeting properties. These characteristics make nanodrug delivery systems synergistically enhance efficacy and reduce toxicity in cancer treatment. In this review, we will introduce the composition of nanoparticle drug delivery system carriers, their advantages in cancer treatment, and focus on the targeting capabilities of nanoparticle drug delivery systems, as well as briefly introduce clinically approved nanodrugs. This provides a theoretical basis and direction for the continuous improvement of drug-loaded nanosystems and the acceleration of clinical translation.
Emerging Nanomaterials Can Even Treat Chronic Wounds: A Review of Evidence on Magnesium-Based Systems.
Shou Y, Zhao X, Yang F … +5 more , Bai X, Gao F, Li Z, Liu Y, Wang Y
Int J Nanomedicine · 2026 · PMID 42220975 · Full text
Chronic wounds remain a severe clinical challenge worldwide due to persistent inflammation, impaired tissue regeneration, and refractory infection control. Recently, magnesium-based materials have garnered tremendous att...
Chronic wounds remain a severe clinical challenge worldwide due to persistent inflammation, impaired tissue regeneration, and refractory infection control. Recently, magnesium-based materials have garnered tremendous attention for chronic wound healing owing to their exceptional biocompatibility, biodegradability, and multifaceted biological functions in remodeling the wound immune microenvironment. Well-established preclinical evidence demonstrates that magnesium and its derivatives facilitate chronic wound repair by regulating inflammatory responses, promoting angiogenesis, enhancing cellular proliferation and migration, and exerting antibacterial effects, thus constructing a favorable microenvironment for tissue regeneration. Emerging (though still partly speculative) findings suggest that degradation products of magnesium, particularly Mg⁺ ions, play a central role in directing immune cell polarization, optimizing endothelial cell activity, and alleviating oxidative stress. Magnesium-based inorganic materials, nanostructured systems, and hybrid platforms integrated with hydrogels or other bioactive components also exhibit outstanding preclinical therapeutic potential. It is important to note that the vast majority of current evidence remains at the preclinical stage, and any interpretation of translational readiness should be made with caution. However, the clinical translation of these materials is still severely restricted by multiple bottlenecks: the lack of precise control over magnesium degradation and Mg⁺ release kinetics, safety risks arising from local pH elevation and hydrogen gas generation, deficient long-term toxicological data, and the absence of standardized evaluation systems for magnesium-based wound dressings. Future research should prioritize the development of tunable and stimuli-responsive delivery systems, deepening mechanistic insights into magnesium-mediated immunomodulation, and incorporating advanced manufacturing technologies to realize personalized therapeutic strategies. Rigorous biosafety evaluations and clinically relevant preclinical models are also imperative. In conclusion, magnesium-based materials stand as a highly promising and versatile strategy for chronic wound repair, holding great potential to be developed as multifunctional platforms that integrate antibacterial, immunoregulatory, and tissue-regenerative properties for clinical translational applications.
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