International Journal Of Nanomedicine[JOURNAL]
Sun
200 papers
Delivery of TCM Monomers Using Blood Cell Membrane Coated Biomimetic Nanoparticles to Target CVD.
Xi JQ, Zhang JQ, Shen YJ … +5 more , Nie ZY, Shen Y, Cao YB, Zhang LC, Li L
Int J Nanomedicine · 2026 · PMID 42403545 · Full text
Cell membrane-coated nanoparticles are receiving increasing recognition for their potential in treating cardiovascular diseases (CVD). This novel drug delivery system, featuring drug-loaded nanoparticles modified by natu...
Cell membrane-coated nanoparticles are receiving increasing recognition for their potential in treating cardiovascular diseases (CVD). This novel drug delivery system, featuring drug-loaded nanoparticles modified by naturally derived cell membranes, is capable of precisely targeting diseased sites, improving drug bioavailability, evading immune surveillance, and prolonging half-life. These targeted and protective behaviors are driven by the preservation of functional surface proteins on the cell membrane, such as CD47 for inhibiting macrophage phagocytosis and specific integrins for targeting disease sites. More importantly, by translating inherent multi-target bioactivities into localized therapeutic outcomes, this biomimetic nanotechnology can significantly improve the drug delivery of TCM monomers, whose therapeutic effects on the treatment of CVD have been widely recognized. However, their clinical translations have historically been restricted by low bioavailability and unfavorable pharmacokinetics. Therefore, this review underscores recent developments in cell membrane-coated nanocarriers for treating CVD. It then highlights the application of traditional Chinese medicine (TCM) monomers delivered via cell membrane-coated nanoparticles in atherosclerosis, thrombosis, myocardial infarction, and ischemic stroke. Finally, this work discusses the challenges for clinical translation of these biomimetic nanocarriers by highlighting the technical complexities of source cell collection, membrane extraction efficiency, and large-scale manufacturing standardization that currently block clinical translation.
Mechanism-Guided Nanoengineered Therapeutic Peptides for Bone Healing.
Zou SQ, Yu JC, Li Y … +2 more , Chai LZ, Ye YJ
Int J Nanomedicine · 2026 · PMID 42403544 · Full text
Bone healing is frequently compromised not by the absence of a single osteogenic factor, but by the breakdown of coordinated biological processes, including inflammatory resolution, vascular invasion, endogenous cell rec...
Bone healing is frequently compromised not by the absence of a single osteogenic factor, but by the breakdown of coordinated biological processes, including inflammatory resolution, vascular invasion, endogenous cell recruitment, matrix mineralization, and remodeling. Therapeutic peptides are attractive for bone repair because they are chemically defined, modular, and readily engineered to encode diverse functions such as immunomodulation, angiogenic activation, osteogenic signaling, antimicrobial activity, and mineral binding. However, in their free or conventionally delivered forms, peptides often suffer from rapid degradation, diffusion, burst release, poor local retention, and inadequate spatiotemporal presentation, limiting their efficacy in complex defects. Nanoengineering provides the missing level of control by converting sequence-defined peptides into retained, clustered, responsive, and matrix-integrated nanoscale signals that can be interpreted by cells within the evolving defect niche. Unlike previous reviews that are typically organized by material platform (eg, hydrogels, scaffolds) or by peptide category (eg, biomimetic, antimicrobial), this Review adopts a mechanism-guided framework that is structured around the sequential biological bottlenecks of bone healing-from inflammatory resolution and vascular invasion to mineralization and remodeling-and critically examines how nanoengineering transforms peptide sequence information into spatiotemporally effective signals at each stage. It first discusses how sequence features encode regenerative potential and how nanoscale presentation determines whether that potential becomes biologically effective. The field is then organized according to the major biological bottlenecks that peptide nanoengineering can overcome, including immuno-osteogenesis, angiogenic-osteogenic coupling, mineralization guidance, and endogenous cell recruitment. Problem-oriented applications in compromised healing are further examined, with emphasis on infected bone defects and osteoporotic bone repair, and it is argued that biomaterialization acts as a mechanism-amplifying extension of peptide nanoengineering by adding four critical functions: retention, geometry, responsiveness, and defect-specific context matching. Finally, emerging opportunities in AI-assisted peptide design, stage-matched delivery, mineralization-guiding nanoarchitectures, and translational validation in load-bearing and nonunion-relevant models are highlighted. Together, this Review positions nanoengineered therapeutic peptides as a promising preclinical platform that may advance toward more targeted and mechanism-informed strategies for bone regeneration.
MRI-Guided Magnetic Micro/Nanorobots for Precision Neurotherapeutics: From Intelligent Navigation and BBB Penetration to Clinical Translation.
Xu S, Fan H, Chen C … +3 more , Li N, Tang B, Han X
Int J Nanomedicine · 2026 · PMID 42403543 · Full text
The rapid advancements in nanotechnology and medical imaging have positioned magnetic resonance imaging (MRI)-guided magnetic micro/nanorobots (MNRs) as a promising platform for integrated diagnosis and treatment of neur...
The rapid advancements in nanotechnology and medical imaging have positioned magnetic resonance imaging (MRI)-guided magnetic micro/nanorobots (MNRs) as a promising platform for integrated diagnosis and treatment of neurological diseases. This review highlights recent progress in MNR development, focusing on fabrication techniques, driving mechanisms, multimodal imaging integration, AI-enabled navigation, blood-brain barrier (BBB) penetration, and disease-specific applications. We analyze biomimetic designs and functional materials for MNRs, including pH- and ROS-responsive degradable materials, liquid metals, and multifunctional coatings.We further examine MRI-based navigation, emphasizing gradient and rotational field control, closed-loop kinematics, and MRI system compatibility. The review also explores AI-assisted multimodal imaging, including MRI, PET, photoacoustic, and fluorescence techniques, alongside the role of deep learning and digital twin models in real-time tracking and path optimization. In addressing the critical challenge of BBB penetration, we review both conventional and emerging strategies. Finally, we assess preclinical findings on the application of MNRs in brain tumors, cerebrovascular diseases, and neurodegenerative disorders. We further highlight how MNR systems improve therapeutic outcomes by enhancing local drug concentrations, enabling spatiotemporally controlled release, and providing real-time imaging feedback, thereby addressing key failure modes of conventional systemic therapies. The review concludes with a critical assessment of translational challenges and a roadmap toward intelligent, personalized neurotherapeutics.
EGCG-Building Nanocarriers for Multitasking Drug Delivery: Design Principles, Therapeutic Opportunities, and Translational Challenges.
Yongvongsoontorn N, Kurisawa M, Chung JE
Int J Nanomedicine · 2026 · PMID 42403542 · Full text
Recent advances in nanotechnology for drug delivery have enabled improved pharmacokinetics, controlled drug release, and enhanced tissue targeting. However, the clinical impact of many nanocarrier systems remains limited...
Recent advances in nanotechnology for drug delivery have enabled improved pharmacokinetics, controlled drug release, and enhanced tissue targeting. However, the clinical impact of many nanocarrier systems remains limited because most carriers exhibit typically low drug loading, resulting in modest therapeutic benefit and concerns related to excipient burden. Conventional nanocarriers are often composed predominantly of pharmacologically inert materials, requiring large carrier doses that may contribute to immune-related effects, undesired tissue accumulation, and manufacturing complexity. Moreover, the traditional drug loading-stability trade-off has long constrained nanocarrier design. These limitations have stimulated increasing interest in therapeutically active carriers, in which the carrier itself contributes to therapeutic efficacy. (-)-Epigallocatechin-3-gallate (EGCG), the major catechin found in green tea, has emerged as a promising molecular building block for such systems. EGCG possesses intrinsic biological activities such as antioxidant, anti-inflammatory, anticancer, and drug resistance-modulating effects. In addition, the polyphenolic structure of EGCG enables diverse molecular interactions, including hydrophobic interaction, π-π stacking, hydrogen bonding, metal coordination, and dynamic boronate-catechol bonding, allowing EGCG to associate with a wide range of therapeutic agents and promote nanoscale assembly in aqueous environments. Through these combined physicochemical and pharmacological properties, EGCG-building nanocarriers integrate structural and therapeutic functions within a single platform. Such systems can achieve relatively high drug loading, reduce reliance on inert excipients, and promote combinational therapeutic effects between carrier and payload, including the modulation of drug resistance pathways. EGCG-building nanocarriers can be constructed either through direct assembly with therapeutic agents or through chemical modification that programs EGCG into hierarchically organized nanostructures. This review provides an up-to-date overview of EGCG-building nanocarriers, highlighting their design principles, nanocarrier architectures, functional advantages, predominantly preclinical and cancer-focused applications, and key challenges for clinical translation.
Chitosan Oligosaccharide-Functionalized Ruthenium-Curcumin Nanodots for Targeted Therapy of Acute Kidney Injury.
Yu Q, Tan XY, Liu X … +2 more , Mao HB, Chen ZG
Int J Nanomedicine · 2026 · PMID 42403541 · Full text
BACKGROUND: Acute kidney injury (AKI) is a critical clinical syndrome with high morbidity and mortality, primarily driven by mitochondrial oxidative stress and tubular epithelial cell apoptosis. Current antioxidant thera...
BACKGROUND: Acute kidney injury (AKI) is a critical clinical syndrome with high morbidity and mortality, primarily driven by mitochondrial oxidative stress and tubular epithelial cell apoptosis. Current antioxidant therapies are limited by poor bioavailability and lack of renal specificity. To address this, we developed a dual-targeting nanomedicine based on ultrasmall chitosan oligosaccharide-functionalized ruthenium-curcumin nanodots (LMWC/Ru-Cur). METHODS: Ru-Cur coordination polymer nanodots were synthesized and subsequently coated with low-molecular-weight chitosan (LMWC). The nanoparticles were characterized for size, surface charge, stability, and antioxidant capacity. In vitro studies using HK-2 cells assessed cytocompatibility, cellular uptake, and protection against HO- or cisplatin-induced injury via measurements of viability, mitochondrial ROS, membrane potential, and apoptosis. In vivo efficacy and biodistribution were evaluated in murine models of ischemia-reperfusion- and cisplatin-induced AKI. RESULTS: The resulting LMWC/Ru-Cur nanodots exhibited uniform size (~7.6 nm), good aqueous stability, and potent broad-spectrum radical scavenging ability. They were efficiently internalized by renal tubular cells via megalin receptor-mediated endocytosis, leading to significantly enhanced renal accumulation. Treatment with LMWC/Ru-Cur attenuated oxidative stress, restored mitochondrial function, reduced apoptosis in injured HK-2 cells, and improved renal function (serum creatinine and blood urea nitrogen), histopathology, and inflammatory cytokine levels in both AKI models, outperforming free curcumin or unmodified Ru-Cur. The nanodots also demonstrated favorable short-term biocompatibility and in vivo biosafety. CONCLUSION: LMWC/Ru-Cur nanodots represent a promising targeted nanotherapeutic strategy for AKI, integrating passive glomerular filtration with active receptor-mediated tubular delivery to effectively mitigate oxidative stress and mitochondrial damage, thereby preserving renal function. This work provides a rational design for metal-polyphenol based nanomedicines in the treatment of acute organ injury.
Magnetic Nanoparticles as a Theranostic Platform in Brain Tumor Treatment: Surmounting the Bench-to-Bedside Barriers.
Zhang F, Wang Y, Wang Q … +6 more , Sun C, Jing Y, Wang S, Shan J, Liu H, Zhu Z
Int J Nanomedicine · 2026 · PMID 42403540 · Full text
Malignant brain tumors, particularly glioblastoma, remain one of the greatest challenges in oncology due to their invasive nature, therapeutic resistance, and protection by the blood-brain barrier. Decades of limited the...
Malignant brain tumors, particularly glioblastoma, remain one of the greatest challenges in oncology due to their invasive nature, therapeutic resistance, and protection by the blood-brain barrier. Decades of limited therapeutic progress underscore the need for new treatment strategies beyond conventional modalities. Magnetic nanoparticles have emerged as a promising theranostic platform that integrates high-precision imaging, targeted delivery, and synergistic therapy. In this review, we outline a mechanistic framework for magnetic nanoparticle applications, with a focus on the link between ferroptosis and immune activation. We discuss how the intrinsic properties of magnetic nanoparticles can be engineered to induce iron-dependent ferroptotic cell death, which may help overcome apoptosis resistance and also trigger immunogenic cell death. This magnetic nanoparticle-induced immunogenic cell death may shift the immunosuppressive brain tumor microenvironment from a "cold" state toward a more immune-active phenotype, thereby supporting combination immunotherapy. We also examine key translational challenges and potential solutions, including quantitative magnetic particle imaging-guided therapeutic dosimetry, focused ultrasound-mediated delivery strategies, and issues related to Chemistry, Manufacturing, and Controls and regulatory science. By analyzing these translational challenges, this review aims to highlight practical considerations for advancing magnetic nanoparticle-based therapies toward clinical neuro-oncology.
Natural Product-Based Nanomicelles: Properties, Fabrication Strategies, and Therapeutic Applications in Diseases.
Yang J, Feng Z, Fu J … +3 more , Huang J, Wang S, Li L
Int J Nanomedicine · 2026 · PMID 42403539 · Full text
Many bioactive natural products suffer from poor water solubility, rapid metabolism, and low bioavailability, which severely limit their clinical application. Natural product‑based nanomicelles (NSNs), which integrate th...
Many bioactive natural products suffer from poor water solubility, rapid metabolism, and low bioavailability, which severely limit their clinical application. Natural product‑based nanomicelles (NSNs), which integrate the delivery functions of nanocarriers with the intrinsic therapeutic activities of the materials themselves, offer a promising solution to this dilemma. NSNs are self‑assembled nanoscale delivery systems constructed from natural small molecules, natural polymers, and their derivatives. This review provides a systematic overview of NSNs. We first summarize their main fabrication strategies, including nanoprecipitation, dialysis, thin‑film hydration, chemical conjugation, and electrostatic interaction, and compare the biological characteristics of NSNs with those of synthetic polymer micelles. The core advantages of NSNs include excellent biocompatibility, intrinsic lesion‑targeting capability, and drug‑excipient synergy. Subsequently, we detail the mechanisms and therapeutic applications of NSNs in six major disease areas: anti‑infection, oncology, inflammation and autoimmune diseases, metabolic diseases, fibrotic diseases, and nervous system disorders. A cross‑disease analysis reveals that modulation of oxidative stress is a common core mechanism underlying the therapeutic benefits of NSNs. Finally, we critically discuss the major barriers to clinical translation, such as batch‑to‑batch variability of natural materials and good manufacturing practice compliance, and propose future directions including mechanism‑driven rational design, theranostics, and manufacturing scalability.
Bioactive Nanocomposite-Mediated Macrophage Metabolic Shift Orchestrates Pro-Regenerative Healing in the Diabetic Wound Microenvironment.
Shen T, Xu X, Guo Z … +6 more , Zhou W, Xiao X, Liao S, Huang J, Liu X, Fan Z
Int J Nanomedicine · 2026 · PMID 42403538 · Full text
INTRODUCTION: Chronic diabetic wounds suffer from persistent oxidative stress, unresolved inflammation, and impaired neovascularization, with limited effective therapies. METHODS: We developed a biomimetic nanocomposite...
INTRODUCTION: Chronic diabetic wounds suffer from persistent oxidative stress, unresolved inflammation, and impaired neovascularization, with limited effective therapies. METHODS: We developed a biomimetic nanocomposite (PEG-HS/TiO) combining antioxidant TiO with sustained-release honeysuckle. In vitro, we evaluated ROS scavenging, cellular senescence, VEGF expression, and macrophage polarization. In vivo, we assessed wound closure, neovascularization, collagen remodeling, and inflammatory markers in a diabetic mouse model. RESULTS: PEG-HS/TiO achieved sustained HS release over 72 hours. It scavenged superoxide and HO, reduced endothelial ROS by approximately 89%, suppressed senescence markers, and restored VEGF expression (>7-fold increase vs. HO control). The nanocomposite shifted macrophages from M1 to M2 phenotype, increasing the CD206/CD86 ratio. In vivo, PEG-HS/TiO accelerated wound closure (76% wound area reduction by day 7 vs. 18% in Sham), enhanced CD31+ vessels (6.3-fold vs. Sham), improved collagen organization, reduced M1 macrophages by 85% and IL-1β by 73%, increased IL-10 by 3.1-fold, and lowered systemic CRP and PCT. DISCUSSION: PEG-HS/TiO breaks the diabetic wound pathology cycle through ROS neutralization, anti-senescence, and macrophage immunometabolic reprogramming, representing a promising strategy for diabetic wound management.
Nanomedicine for Depression: From Blood-Brain Barrier Delivery to Neuroimmune-Barrier-Plasticity Network Reprogramming.
Wang X, Shen L, Mo Q … +5 more , Wang X, Wang B, Chen J, Teng Y, Zhang Z
Int J Nanomedicine · 2026 · PMID 42403537 · Full text
Depression is a heterogeneous and recurrent brain disorder in which neuroinflammation, blood-brain barrier dysfunction, oxidative and mitochondrial stress, and impaired neuroplasticity interact within the neurovascular-g...
Depression is a heterogeneous and recurrent brain disorder in which neuroinflammation, blood-brain barrier dysfunction, oxidative and mitochondrial stress, and impaired neuroplasticity interact within the neurovascular-glial-neuronal unit. This mechanism-oriented integrative review examines how engineered nanosystems may move beyond brain entry toward lesion-directed modulation of the neuroinflammation-barrier-neuroplasticity axis. We first synthesize the pathological nodes that sustain depression-related network dysfunction and then classify current nanotherapeutic strategies into three categories: small-molecule nanodelivery systems, nucleic acid nanocarriers, and functional nanoplatforms, including lipid and polymeric nanoparticles, inorganic and nanozyme-based systems, biomimetic membrane-coated nanoparticles, and engineered extracellular vesicles, including exosomes. Unlike previous nanosynthesis-focused or catalogue-style nanocarrier reviews, this review organizes the field around a disease-mechanism framework rather than material type alone, emphasizing barrier-state navigation, glial-neuronal-subcellular targeting, stimulus-responsive release, and coordinated modulation of inflammation, vascular integrity, redox homeostasis, and synaptic plasticity. We further argue that nanoplatforms should be evaluated not only by brain accumulation but also by patient stratification, engagement of defined pathological nodes, multimodal biomarker evidence of network-level modulation, manufacturability, and safety under repeated administration. Major translational bottlenecks include insufficient subtype-specific patient selection, limited human relevance of current stress- and inflammation-based models, uncertain biodistribution and long-term neurotoxicity, constraints in scaling up nose-to-brain delivery, batch-to-batch variability, cargo instability, immunogenicity, and unclear regulatory classification of complex biologic or combination products. Finally, we propose a pathological-network-guided precision nanomedicine framework that integrates blood-brain barrier status assessment, liquid biopsy and imaging biomarkers, human-relevant validation models, and scalable quality control to guide future platform design and clinical translation. This review provides a disease-mechanism-centered roadmap for transforming nanomedicine for depression from delivery optimization into precision network-oriented intervention.
Trastuzumab-Conjugated Nanoliposomes for Targeted Capecitabine Delivery to Suppress HER2-Positive Breast Tumor: Efficacy Analysis in NOD SCID Mice Xenografts.
Das S, Satapathy BS, Rahamathulla M … +7 more , Alhamhoom Y, Pattanaik S, Chawla S, Pattnaik G, Rath D, Ahmed MM, Pasha I
Int J Nanomedicine · 2026 · PMID 42403536 · Full text
INTRODUCTION: Treatment of advanced breast cancer has proven to be difficult. Routine chemotherapy has limitations due to unavoidable and dreaded adverse effects during and after treatment, necessitating the development...
INTRODUCTION: Treatment of advanced breast cancer has proven to be difficult. Routine chemotherapy has limitations due to unavoidable and dreaded adverse effects during and after treatment, necessitating the development of tailored therapies. Capecitabine is a commonly used anticancer drug that comes in tablet form for oral administration. However, high doses and frequent administration-related toxicities limit its efficacy in HER2-positive breast cancer patients. METHODS: The current work seeks to target capecitabine using experimental nanoliposomes coupled to trastuzumab (TZ) (HER2-targeting monoclonal antibody) and assess anticancer activity in a NOD SCID mice xenograft model of breast cancer. Experimental capecitabine-loaded trastuzumab-nanoliposomes (TZ-CNLs) were developed by a previously reported method. FESEM, AFM, TEM, zeta potential, and drug release studies were used to characterize TZ-CNLs. In vivo effectiveness of CNLs/TZ-CNLs was carried out in experimental mice and compared with the free capecitabine-treated group. Hematological, biochemical, and histopathological analyses of experimental CNLs/TZ-CNLs were conducted across different treatment groups compared with the control. RESULTS: Experimental TZ-CNLs were spherical, smooth, and uniformly distributed, with an average size (198.6 nm), a zeta potential (-27.91 mV), and a drug loading (9.6±0.51%). The AFM indicated that TZ conjugation had no effect on texture. TZ-CNLs released 81.5 ± 3.05% capecitabine after 96 h, compared to CNLs/free capecitabine. After 12 days of treatment, TZ-CNLs significantly reduced tumor development (97.91 ± 3.0 mm) compared to unconjugated CNLs/free capecitabine in NOD SCID mice xenografts. The enhanced antitumor activity observed with TZ-CNLs is consistent with HER2-targeted delivery mediated by TZ conjugation. Furthermore, TZ-CNL-treated animals maintained a healthier body-weight profile compared with free capecitabine and CNL-treated groups, suggesting improved treatment tolerability and reduced systemic toxicity. Plasma pharmacokinetic analysis indicated that administration of TZ-CNL-3 resulted in greater systemic availability of capecitabine, as well as prolonged mean residence time and increased volume of distribution, compared to free capecitabine and CNL-3. The study depicted an overall improvement in key biochemical parameters toward normal in animals treated with TZ-CNLs. CONCLUSION: Overall, the promising preclinical outcomes, including tumor inhibition, improved hematologic and biochemical safety indices, and maintenance of organ histopathology, support the need for future preclinical investigations to determine whether TZ-CNLs may have application in HER2-positive breast cancer therapy.
Dual-Metal Organic Framework Nanozyme for Synergistic Photothermal-Chemodynamic Therapy: Copper-Molybdenum Synergism in Gastric Cancer Treatment.
Sun D, Linghu B, Lu C … +1 more , Wei B
Int J Nanomedicine · 2026 · PMID 42403535 · Full text
PURPOSE: To address the dual challenges of chemotherapy toxicity and poor tumor microenvironment regulation in gastric cancer, we developed a copper-molybdenum bimetallic organic framework nanozyme (CMP) that integrates...
PURPOSE: To address the dual challenges of chemotherapy toxicity and poor tumor microenvironment regulation in gastric cancer, we developed a copper-molybdenum bimetallic organic framework nanozyme (CMP) that integrates chemodynamic therapy (CDT) and photothermal therapy (PTT). The system leverages synergistic reactive oxygen species (ROS) generation and localized hyperthermia to deliver efficient, low-toxicity treatment. METHODS: The CMP nanodrug was synthesized by encapsulating Keggin-type phosphomolybdic acid (HPMo O ) into copper-based MOF pores via hydrothermal reaction. Physicochemical properties were characterized using transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Systematic evaluation of antitumor efficacy and biosafety was conducted through in vitro assays (CCK-8, calcein-AM/PI staining, ROS detection) and in vivo xenograft models (subcutaneous implantation of NCI-N87 cells in BALB/c nude mice). RESULTS: The CMP nanozyme demonstrated exceptional photothermal conversion efficiency (29.4% under 808 nm laser). In vitro experiments revealed significant cytotoxicity with ROS elevation. In vivo studies showed significant tumor growth inhibition without hematotoxicity (WBC, ALT levels showed no statistical significance vs. controls). Histopathology confirmed extensive tumor necrosis with preserved cytoarchitecture in vital organs (heart, liver, spleen, and kidney). CONCLUSION: The CMP nanozyme achieves potent antitumor efficacy through photothermal-enhanced Fenton-like reactions, depleting glutathione and amplifying ROS. It suppresses gastric cancer in vivo with minimal systemic toxicity, representing a promising nanoplatform for precision therapy.
Physicochemical Stability and Cross-Context Validation of PEGylated Human Serum Albumin Nanoparticles for Dual Neurotrophin Delivery in the Rabbit Eye and Oxidative Stress Models.
Stukan I, Dąbkowska M, Machalińska A … +12 more , Łuczkowska K, Pukacka K, Wasilewska M, Stodolak P, Winiarczyk M, Winiarczyk D, Zwolska J, Kuduk B, Szadkowski M, Balicki I, Kawa MP, Machaliński B
Int J Nanomedicine · 2026 · PMID 42403534 · Full text
PURPOSE: Neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) exhibit pro-survival and homeostatic properties, but their clinical translation is limited by protein instability and rapid...
PURPOSE: Neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) exhibit pro-survival and homeostatic properties, but their clinical translation is limited by protein instability and rapid clearance. We evaluated a PEGylated human serum albumin (HSA) nanoparticle system for BDNF/NT3 co-delivery, focusing on physicochemical stability, ocular biodistribution in the rabbit eye, intracellular protein delivery, and protection against oxidative stress-associated cellular damage in human cells. MATERIALS AND METHODS: PEGylated HSA-BDNF-NT3 nanoparticles with nominal neurotrophin concentrations of 5 µg/mL (NeO5) or 10 µg/mL (NeO10) were generated by spontaneous self-assembly and characterized using multiangle dynamic light scattering, electrophoretic light scattering, and atomic force microscopy. In vivo performance was assessed after intravitreal injection in rabbits by enzyme-linked immunosorbent assay (ELISA)-based protein quantification and exploratory reverse transcription quantitative polymerase chain reaction (RT-qPCR) profiling of survival-, proliferation-, and apoptosis-related genes. Functional delivery was examined in sodium iodate-stressed ARPE-19 and 6-hydroxydopamine-stressed retinoic acid-differentiated SH-SY5Y cells using ELISA assays, JC-1 analysis, Annexin V/ propidium iodide flow cytometry, high-performance liquid chromatography for malondialdehyde quantification, and RT-qPCR. RESULTS: Both formulations formed stable, spherical nanoparticles (5.9-54.2 nm) with low polydispersity index (≈ 0.18) and preserved colloidal integrity over 28 days. In vivo, BDNF was detectable in ocular tissues up to 72 h and RT qPCR did not reveal a coordinated pro-apoptotic response under the tested conditions. In vitro, nanoparticle treatment significantly increased intracellular BDNF and NT3 levels, improved viability, reduced apoptotic cell fractions, and markedly decreased lipid peroxidation, particularly for NeO10. Increased tropomyosin receptor kinase B and cAMP response element-binding protein expression provided supportive molecular evidence consistent with neurotrophin-related cellular responses. CONCLUSION: PEGylated HSA nanoparticles enable stable neurotrophin loading, efficient intracellular delivery, and attenuation of oxidative stress-induced cytotoxicity. These findings support further development of albumin-based nanocarriers for translational nanomedicine applications.
Extracellular Vesicle-Associated Non-Coding RNAs in Preeclampsia: Mechanistic Insights, Biomarker Discovery, and Emerging Nanomedicine Concepts.
Zhang Z, Du J, Chen T … +9 more , Teng Y, Chen J, Li Y, Zhang Y, Long Y, Li C, Wu Z, Li N, Yang Z
Int J Nanomedicine · 2026 · PMID 42403533 · Full text
Preeclampsia (PE) is a complex multisystem disorder that affects 2-8% of pregnancies worldwide and poses substantial risks to maternal and fetal health. Current diagnostic approaches rely largely on clinical signs and an...
Preeclampsia (PE) is a complex multisystem disorder that affects 2-8% of pregnancies worldwide and poses substantial risks to maternal and fetal health. Current diagnostic approaches rely largely on clinical signs and angiogenic biomarkers, and available treatments remain primarily supportive; they do not directly reverse the placental or systemic mechanisms that drive the disease. Extracellular vesicles (EVs), including small EVs often termed exosomes, carry non-coding RNAs (ncRNAs) that may contribute to placental-maternal communication in both normal and pathological pregnancy. In PE, altered EV-associated microRNAs, long non-coding RNAs, and circular RNAs have been detected in placental tissues, trophoblast-derived systems, maternal plasma or serum, urine, amniotic fluid, and other pregnancy-related samples. However, these matrices should not be assumed to indicate definitive tissue or cellular origins without appropriate source-attribution methods. This review summarizes current evidence on EV-associated ncRNAs in PE from three perspectives: mechanistic studies, biomarker discovery, and exploratory nanomedicine strategies. First, we discuss how dysregulated EV-associated ncRNAs may contribute to trophoblast dysfunction, immune-inflammatory imbalance, endothelial injury, and angiogenic dysregulation. Second, we evaluate EV-associated ncRNAs as candidate liquid-biopsy biomarkers, emphasizing that most reported signatures remain at the discovery or early validation stage. Their clinical implementation will require standardized EV isolation, RNA profiling, normalization procedures, and validation in independent longitudinal cohorts. Third, we discuss engineered EVs and EV-mimetic nanocarriers as experimental platforms for ncRNA delivery and distinguish these preclinical therapeutic concepts from clinically established PE management. Rather than suggesting immediate diagnostic or therapeutic readiness, this review highlights the opportunities and limitations of EV-associated ncRNAs as a framework for future PE research. Key challenges include EV heterogeneity, limited discrimination among vesicular subtypes, uncertain tissue origins of circulating EV cargo, poor reproducibility across cohorts, safety concerns during pregnancy, scalable manufacturing, and ethical considerations related to maternal-fetal interventions. Future studies integrating rigorously characterized EV populations, multi-omics profiling, functional validation, and longitudinal clinical sampling are essential to determine whether EV-associated ncRNAs can be translated into reliable PE biomarkers or safe nanomedicine-based interventions.
The Application of Nanomaterials in the Detection of Liver Cancer Biomarkers.
Qiu D, Cao W, Gao Y … +9 more , Ma T, Deng W, Wang S, Zhang Y, Wei X, Yao L, Gao Z, Wang S, Li M
Int J Nanomedicine · 2026 · PMID 42403532 · Full text
Liver cancer is one of the malignant tumors with high global incidence and mortality rates, with hepatocellular carcinoma (HCC) accounting for 90% of primary liver cancer cases. Due to the lack of specific symptoms in ea...
Liver cancer is one of the malignant tumors with high global incidence and mortality rates, with hepatocellular carcinoma (HCC) accounting for 90% of primary liver cancer cases. Due to the lack of specific symptoms in early-stage liver cancer, diagnosis is often delayed, leading to the majority of patients being identified at intermediate to advanced stages with poor prognoses. Early diagnosis is critical for improving patient survival; however, conventional diagnostic methods face limitations such as low sensitivity and insufficient specificity. Nanomaterials have demonstrated great potential in laboratory research to overcome the limitations of traditional detection technologies by virtue of their unique physicochemical properties. However, most of these relevant studies are still in the laboratory stage and require large-scale clinical validation. This review systematically summarizes the innovative applications of nanomaterials in liver cancer biomarker diagnostics, focusing on their mechanisms for improving detection performance, including signal amplification, targeted recognition, and system optimization. It highlights specific applications of nanomaterials in biomarker detection, discusses current challenges in nanodiagnostic technologies, and explores future development trends, aiming to provide novel perspectives for the diagnosis of liver cancer patients.
Preclinical Advances in Functionalized Nanozymes for Periodontitis: From Antibacterial Action to Tissue Regeneration.
Chen X, Huang L, Lin W … +3 more , Liu M, Jiang Y, Xiao Y
Int J Nanomedicine · 2026 · PMID 42388221 · Full text
BACKGROUND: Periodontitis is a chronic infectious disease caused by bacteria, which leads to destruction of periodontal tissues, tooth loss, and systemic complications. Conventional treatments often fail to counteract th...
BACKGROUND: Periodontitis is a chronic infectious disease caused by bacteria, which leads to destruction of periodontal tissues, tooth loss, and systemic complications. Conventional treatments often fail to counteract the suppression of periodontal tissue regeneration caused by the persistent inflammatory microenvironment. SCOPE: This review focuses on the application of functionalized nanozymes in the treatment of periodontitis, covering the classification of nanozymes, their mechanisms of action, and recent advances in nanozyme-based therapeutic strategies. KEY FINDINGS: Functionalized nanozymes, with their multiple bioactivities including antibacterial, antioxidant, and osteogenic stimulation, represent a promising complement to existing therapeutic approaches. Their sophisticated designs enhance biofilm eradication, modulate immune responses, and facilitate tissue regeneration, thereby overcoming key limitations of existing periodontal treatments. CONCLUSION: Functionalized nanozymes, particularly motor-based composite nanozymes, show great promise for periodontitis treatment due to their self-propulsion and multifunctional design (antibacterial, antioxidant, osteogenic). However, long-term biosafety, especially metal-ion accumulation, remains the key bottleneck for clinical translation. With continued optimization and standardized safety evaluation, these nanozyme platforms may open a new precision therapy avenue for drug-resistant refractory periodontitis.
Advanced Multiscale Inhalation Platforms for Treatment of Pulmonary Diseases.
Zhou S, Ran S, Zhang F … +4 more , Ma H, Jiang C, Li S, Zhang Q
Int J Nanomedicine · 2026 · PMID 42388220 · Full text
Pulmonary diseases, including chronic obstructive pulmonary disease, asthma, pneumonia, pulmonary fibrosis, and lung cancer, pose a significant threat to global health. Their high incidence and mortality rates highlight...
Pulmonary diseases, including chronic obstructive pulmonary disease, asthma, pneumonia, pulmonary fibrosis, and lung cancer, pose a significant threat to global health. Their high incidence and mortality rates highlight the urgency for novel therapeutic approaches. Traditional treatments such as oral and injection administrations face limitations like first-pass effects, low bioavailability, and systemic toxicity, which restrict their therapeutic efficacy. Inhaled preparations, with advantages such as uniform drug distribution, rapid onset, high bioavailability, and avoidance of hepatic first-pass effects, have become effective means for treating lung diseases. This article reviews the research progress of novel inhaled preparations (nanoparticles, liposomes, microspheres, biomimetic platforms) in treating lung diseases, aiming to explore the development and application of novel inhaled formulations driven by advancements in nanotechnology, biomaterials and preparation processes, thereby providing new possibilities for lung disease treatment. Overall, the research and application prospects of novel inhaled preparations are broad, promising more effective and safer treatment options for patients with pulmonary diseases.
Extracellular Vesicles for Therapeutic Applications: A Translational Framework Integrating Sources, Administration Routes, Indications, Quality Control, and Regulatory Systems.
Zhang F, Xing L, Chu W … +5 more , Wang Q, Sun H, Liu Y, An G, Liang X
Int J Nanomedicine · 2026 · PMID 42383231 · Full text
Extracellular vesicles (EVs) are nanoscale membranous vesicles that mediate intercellular communication via the transport of bioactive cargos. With context-dependent intrinsic targeting, source- and cargo-dependent favor...
Extracellular vesicles (EVs) are nanoscale membranous vesicles that mediate intercellular communication via the transport of bioactive cargos. With context-dependent intrinsic targeting, source- and cargo-dependent favorable biocompatibility and loading capacity, EVs represent promising acellular therapeutic platforms with context-dependent translational potential. However, their clinical application is hindered by source-associated functional heterogeneity, unclear matching relationships between administration routes and disease indications, as well as imperfect quality control specifications and fragmented global regulatory frameworks alongside insufficient clinical trial data. This review systematically summarizes the biological features of EVs originating from mesenchymal stem cells, immune cells, tumor cells, plants, milk, microbes and platelets, and compares the pros and cons and applicable scenarios of intravenous, oral, nasal, inhaled, and multiple local injection delivery modalities. We further recapitulate the research progress of EV therapeutics across regenerative medicine, immunotherapy, oncology, neurological and metabolic disorders, and analyze worldwide regulatory policies while sorting out the up-to-date industrial-sponsored global clinical pipeline updated to April 2026. Centered on a core five-dimensional matching framework integrating EV sources, administration routes, disease indications, critical quality attributes (CQAs) and global regulatory requirements, this work elaborates current translational bottlenecks and commercialization obstacles of EV products. This review provides theoretical support for precision EV therapy optimization, unified quality criterion establishment, international regulatory coordination and accelerated clinical and industrial transformation of EV-based medicines.
Exosome-Biomaterial Platforms for Diabetic Skin Infections: Microenvironment Remodeling, Responsive Delivery, and Clinical Translation.
Xiao J, He Z, Bu Y … +2 more , Lu Y, Liang S
Int J Nanomedicine · 2026 · PMID 42383230 · Full text
Diabetic skin infections, particularly diabetic foot ulcers (DFU), remain difficult to treat because infection, biofilm formation, persistent inflammation, oxidative stress, hypoxia, impaired angiogenesis, and extracellu...
Diabetic skin infections, particularly diabetic foot ulcers (DFU), remain difficult to treat because infection, biofilm formation, persistent inflammation, oxidative stress, hypoxia, impaired angiogenesis, and extracellular matrix (ECM) disruption coexist within a hostile wound microenvironment. Conventional treatments, including antibiotics, surgical debridement, negative pressure wound therapy, and standard dressings, are indispensable but often fail to simultaneously suppress infection and restore regenerative healing. Exosomes have emerged as promising acellular mediators for diabetic wound repair because they can coordinate immune regulation, angiogenesis, matrix remodeling, and re-epithelialization. However, direct exosome administration is limited by rapid clearance, poor local retention, dilution by wound exudate, dose inconsistency, and manufacturing heterogeneity. Biomaterial platforms, including hydrogels, microneedle patches, membranes, cryogels, porous scaffolds, and responsive nanocomposite systems, provide a rational strategy to protect exosome bioactivity, prolong local retention, and enable sustained or stimulus-responsive release. More importantly, these materials can be engineered to actively regulate infection-associated pathological barriers, including biofilm persistence, excessive oxidative stress, hypoxia, and impaired tissue reconstruction. This review summarizes recent advances in exosome-biomaterial systems for diabetic skin infections, with emphasis on delivery design, microenvironment-responsive release, anti-infective and regenerative mechanisms, platform comparison, and clinical translation. We further discuss key translational challenges, including exosome source selection, dose standardization, potency assays, scalable manufacturing, storage stability, biosafety, regulatory classification, and clinical trial design. Current evidence suggests that exosome-biomaterial systems can improve wound closure, vascularization, collagen deposition, re-epithelialization, and infection control in preclinical models. Nevertheless, high-quality clinical evidence remains limited. Future studies should prioritize clinically relevant infected diabetic wound models, standardized quality-control frameworks, and simplified delivery systems compatible with routine wound care.
Diosmin-Capped Silver Nanoparticles Promote Osteogenic Differentiation of Human Periodontal Ligament Stem Cells: Box-Behnken Optimization and in vitro Evaluation.
Abdel Gawad R, Hatem S, I Rizk N … +4 more , N Raafat S, E Ali D, A El-Shiekh R, H Shakshak D
Int J Nanomedicine · 2026 · PMID 42376637 · Full text
AIM: Diosmin is a bioactive flavonoid with anti-inflammatory, anti-oxidant, and osteogenic properties; however, its poor water solubility limits its therapeutic use. To overcome this, the study developed Diosmin-loaded s...
AIM: Diosmin is a bioactive flavonoid with anti-inflammatory, anti-oxidant, and osteogenic properties; however, its poor water solubility limits its therapeutic use. To overcome this, the study developed Diosmin-loaded silver nanoparticles (AgNPs), leveraging the bone-regenerative potential of silver, as a unique strategy to improve the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). METHODS: The nanoparticles loaded with the extracted Diosmin were prepared using a scalable green reduction method and optimized using the Box-Behnken design (BBD) and response surface methodology. Key factors (silver nitrate concentration, Diosmin concentration, and reaction temperature) were assessed for their effects on the particle size, zeta potential, and polydispersity index. This study also evaluated the effects of Diosmin-loaded AgNPs on the viability and osteogenic differentiation of human PDLSCs. Alizarin Red staining and alkaline phosphatase activity were used to assess osteogenic differentiation. Moreover, real-time quantitative polymerase chain reaction (RT-qPCR) was used to track the expression of osteogenic-associated markers, osteoprotegerin (OPG) and runt-related transcription factor 2 (RUNX2), as well as proinflammatory markers, TNF-α and IL-1β. RESULTS: The optimized Diosmin-loaded AgNPs identified by the BBD showed high desirability, with particle size of 181.0±8.45 nm using dynamic light scattering technique (DLS) and a negative surface charge of -21.45±1.27 mV, confirmed by transmission electron microscopy (TEM) photomicrographs. Moreover, energy-dispersive X-ray (EDX) analysis showed the preparation of AgNPs through showing their elemental peaks. Stability studies demonstrated that formulations remained stable at 4.0±2.0°C for up to 3 months. The results showed that, in contrast to silver nitrate (AgNO), Diosmin-loaded AgNPs promoted osteogenic differentiation and modulated the expression of inflammatory markers, indicating a potential role in the regulation of the local inflammatory microenvironment associated with osteogenesis. CONCLUSION: Green AgNPs have proven their efficacy as a potential approach for osteogenic differentiation.
Surfactant-Engineered Niosomal Antibiotic Systems for Biofilm-Associated Infections: Design Principles and Translational Perspectives.
Rahma S, Amalia E, Kusuma SAF
Int J Nanomedicine · 2026 · PMID 42376636 · Full text
Persistent microbial biofilm infections remain a major obstacle to effective antimicrobial therapy due to restricted drug diffusion, metabolic heterogeneity, and the presence of tolerant bacterial subpopulations. In devi...
Persistent microbial biofilm infections remain a major obstacle to effective antimicrobial therapy due to restricted drug diffusion, metabolic heterogeneity, and the presence of tolerant bacterial subpopulations. In device-associated infections, biofilms substantially reduce antibiotic efficacy and contribute to chronic relapse despite adequate systemic exposure. Although nanocarrier-based delivery systems have been widely investigated, many formulations remain empirically developed with insufficient consideration of biofilm-specific physicochemical and biological barriers. This review examines surfactant-engineered niosomal antibiotic systems from a rational design perspective. Key formulation parameters, including surfactant type, hydrophile-lipophile balance (HLB), cholesterol content, surface charge, and microenvironment-responsive behavior, critically influence bilayer rigidity, permeability, encapsulation efficiency, intrabiofilm transport, and release kinetics. In particular, electrostatic interactions with the negatively charged extracellular polymeric substance (EPS) matrix and pH-responsive destabilization strategies are discussed as important determinants of localized antibiotic delivery within heterogeneous biofilm environments. Despite promising antibiofilm activity in vitro, translational progress remains limited by variability in formulation characterization, insufficient in vivo validation, and incomplete alignment between carrier responsiveness and biofilm microenvironmental conditions. By integrating insights from pharmaceutics, materials science, and microbial pathophysiology, this review proposes a structured framework for the rational design of surfactant-engineered niosomes and highlights key considerations for advancing antibiofilm nanomedicine.
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