International Journal Of Nanomedicine[JOURNAL]
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200 papers
Stimuli-Responsive Nasal in situ Gel Drug Delivery Systems: from Material Design to Clinical Translation.
He J, Wei J, Chen J … +3 more , Liu T, Long H, Wei W
Int J Nanomedicine · 2026 · PMID 42052513 · Full text
As a novel drug delivery system responsive to environmental stimuli (temperature, pH, ionic strength, etc). nasal in situ gels undergo phase transition to provide breakthrough solutions for precision and long-term manage...
As a novel drug delivery system responsive to environmental stimuli (temperature, pH, ionic strength, etc). nasal in situ gels undergo phase transition to provide breakthrough solutions for precision and long-term management of nasal disorders through the integration of targeted therapy and sustained-release technology. Following nasal administration, the liquid formulation rapidly transforms into a semi-solid gel depot on the mucosal surface, significantly prolonging drug residence time and reducing drug loss due to mucociliary clearance. This process enhances local drug concentration and therapeutic persistence. Incorporating mucoadhesive technology and controlled-release drug-loading systems, this platform enables precise delivery of anti-inflammatory, antihistaminic, and immunomodulatory agents to lesion sites. It effectively mitigates systemic side effects (e.g. drowsiness, hepatic/renal burden) associated with conventional dosage forms while reinforcing nasal mucosal barrier repair. Clinical studies confirm its superior efficacy and safety profile in conditions requiring long-term therapy, including allergic rhinitis, sinusitis, and central nervous system disorders. Its mild gelation properties enhance patient tolerance, and single/every-other-day dosing regimens significantly improve compliance. Further optimization of release kinetics through multi-level drug-loading techniques (e.g. composite nanoparticles) demonstrates potential in gene therapy and vaccine delivery. This review systematically examines material design strategies, drug release mechanisms, clinical advancements, and translational challenges, with focused analysis on the impact of gelation kinetics on delivery efficiency, bottlenecks in scaled-up production. The work aims to provide theoretical foundations for optimized design and clinical translation while exploring future prospects for multifaceted applications in the era of precision medicine.
Cyclodextrin-Based Nanogels with Chemistry-Tunable Intracellular Stability and Distribution.
Zhang R, Ji Y, van Rijn P
Int J Nanomedicine · 2026 · PMID 42052512 · Full text
INTRODUCTION: Cyclodextrin-based nanogels (CD-nGels) uniquely enable encapsulation of hydrophobic pharmaceuticals within hydrophilic networks through host-guest interactions, thereby improving drug solubility, stability,...
INTRODUCTION: Cyclodextrin-based nanogels (CD-nGels) uniquely enable encapsulation of hydrophobic pharmaceuticals within hydrophilic networks through host-guest interactions, thereby improving drug solubility, stability, and therapeutic efficacy. METHODS: Here, we report the surfactant-free synthesis of Nile Blue-labeled fluorescent CD-nGels with tunable hydrolytic properties by integrating amide or ester linkages in both β-cyclodextrin (βCD) moieties and crosslinking sites. Three formulations were prepared with progressively increasing hydrolytic sensitivity: NG1 (fully amide-linked), NG2 (ester-functionalized βCD with amide crosslinking), and NG3 (ester linkages in both βCD and crosslinker domains). RESULTS: The resulting CD-nGels were monodisperse with hydrodynamic diameters ranging from 247 to 431 nm. Hydrolysis study in mildly acidic conditions (pH 5.1) and in intracellular-mimicking MCF-7 lysate demonstrated that the structural stability is predominantly dictated by chemical compositions. Coumarin-6 (C6), a hydrophobic fluorescent model drug, was efficiently encapsulated via host-guest interactions to visualize the intracellular redistribution after cellular uptake. The confocal microscopy revealed that the three CD-nGel formulations exhibited progressively enhanced intracellular degradability, leading to distinct intracellular fluorescence distributions: while the fully amide-linked NG1 maintained a compact intracellular fluorescence pattern, the ester-containing NG2 and NG3 exhibited progressively diffuse cytoplasmic signals consistent with reduced structural stability. DISCUSSION: Overall, this modular platform enables chemical tuning of intracellular stability and distribution of CD-nGels, providing a design basis for the future development of CD-based nGels for controlled intracellular drug delivery applications.
CXCR4-Targeted Nanotherapeutics: A Promising Approach for Liver Fibrosis and Hepatocellular Carcinoma Management.
Ullah A, Khan M, Zhang Y … +7 more , Shafiq M, Ullah M, Abbas A, Ullah K, Xiangxiang X, Chen G, Diao Y
Int J Nanomedicine · 2026 · PMID 42046739 · Full text
CXCR4 plays a pivotal role in liver fibrosis (LF) by mediating the activation of hepatic stellate cells (HSCs), which contribute to extracellular matrix (ECM) deposition and scar formation. The CXCR4/CXCL12 axis is essen...
CXCR4 plays a pivotal role in liver fibrosis (LF) by mediating the activation of hepatic stellate cells (HSCs), which contribute to extracellular matrix (ECM) deposition and scar formation. The CXCR4/CXCL12 axis is essential in fibrogenesis, promoting HSCs activation, inflammation, and angiogenesis, which exacerbates fibrosis and creates an environment conducive to hepatocellular carcinoma (HCC) development. In HCC, CXCR4 signaling supports tumor cell proliferation, survival, and metastasis, linking chronic liver injury to cancer progression. Recent advancements in targeted drug delivery have facilitated the development of CXCR4-targeted therapies, improving treatment efficacy while minimizing systemic toxicity. This review examines the interactions between CXCR4 and its ligand CXCL12, the associated signaling pathways, and their role in LF and HCC. Furthermore, it explores CXCR4 as a therapeutic target, focusing on CXCR4 blockers, peptide inhibitors, and gene silencing/editing strategies. The review also highlights various CXCR4-targeted nano therapeutic strategies, such as liposomes, lipid NPs, microbubbles, polymeric NPs incorporating siRNA, miRNA, small molecules, peptides etc for the management of LF and HCC. Additionally, the review addresses the clinical progress of monoclonal antibodies, small molecules, and peptides targeting CXCR4 in both preclinical and clinical trials. Challenges and future directions of CXCR4-targeted nanotherapeutic are also discussed. In conclusion, this review emphasizes the therapeutic potential of CXCR4-targeted nanotherapeutic strategies for combating LF and HCC.
Nanotherapeutic Strategies for Osteoarthritis: Targeting Aging, Metabolism and Inflammation.
He Z, Chen Y, Zhao K … +6 more , Jiao Y, Ji Y, Mao D, Wan R, Zhang J, Hu Y
Int J Nanomedicine · 2026 · PMID 42046738 · Full text
Osteoarthritis (OA) is no longer viewed as a mere "wear-and-tear" disease, but rather as a multifactorial joint failure syndrome driven by cellular senescence, metabolic dysregulation, and low-grade chronic inflammation....
Osteoarthritis (OA) is no longer viewed as a mere "wear-and-tear" disease, but rather as a multifactorial joint failure syndrome driven by cellular senescence, metabolic dysregulation, and low-grade chronic inflammation. These pathological pillars synergistically disrupt cartilage homeostasis, subchondral bone remodeling, and synovial inflammation, collectively fueling disease progression. While conventional therapies offer only symptomatic relief, they fail to reverse or reprogram the underlying pathological microenvironment. Consequently, there is an urgent need to develop disease-modifying interventions that can simultaneously target these pathological pillars. Here, we critically examine how nanomaterial-based platforms-leveraging tailorable surface chemistry, cartilage-penetrating dimensions, and stimuli-responsive cargo release-enable precision targeting of these interconnected mechanisms. We highlight advances in senolytic delivery for senescent cell clearance, redox-modulating nanozymes for metabolic reprogramming, and immunoregulatory strategies for macrophage repolarization, emphasizing designs that transcend passive drug delivery to actively remodel the joint microenvironment. By integrating mechanistic insights with engineering innovation, this review outlines a roadmap for next-generation disease-modifying nanomedicines that promise not merely to slow OA progression, but to restore the biological clock of the joint. We also discuss current translational barriers and propose future directions for personalized OA therapy.
Mesenchymal Stem Cells Membrane Biomimetic Nanoplatform for Glioblastoma-Targeted Combinatorial Chemotherapy.
Li Y, Jin T, Guan X … +4 more , Han C, Zou W, Shen L, Liu J
Int J Nanomedicine · 2026 · PMID 42046737 · Full text
INTRODUCTION: Glioblastoma, the most aggressive form of brain tumor, continues to present significant therapeutic challenges, including the limited delivery of drugs posed by the blood-brain barrier (BBB) and the blood-b...
INTRODUCTION: Glioblastoma, the most aggressive form of brain tumor, continues to present significant therapeutic challenges, including the limited delivery of drugs posed by the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB), severe systemic toxicity associated with conventional chemotherapy, and the complexity arising from tumor heterogeneity. METHODS: To overcome these challenges, this study developed a novel biomimetic drug delivery system. Specifically, we prepared poly(lactic-co-glycolic acid) (PLGA) nanoparticles co-loaded with the chemotherapeutic agent doxorubicin (DOX) and the natural polyphenol curcumin (CUR), and subsequently functionalized them with the membrane of human umbilical cord mesenchymal stem cells (hUC-MSCs), which possess inherent tumor-homing capability. RESULTS: In vitro studies demonstrated that the hUC-MSCs membrane coating significantly enhanced targeted recognition and cellular uptake by glioblastoma cells, and the biomimetic nanoplatform exhibited superior synergistic cytotoxicity and induced greater cellular apoptosis compared to free drug combinations and uncoated nanoparticles. Antitumor mechanism analysis indicated that biomimetic nanoplatform inhibited glioblastoma migration, invasion, and angiogenesis. In vivo anti-tumor efficacy studies showed that the biomimetic nanoparticles effectively suppressed the growth of tumor. Notably, CUR contributed to the system by amplifying the anticancer activity of DOX and alleviating its associated toxicity. DISCUSSION: This work demonstrates that hUC-MSC membrane-camouflaged PLGA nanoparticles enable successful co-delivery of DOX and CUR, offering a promising strategy to address the critical barriers of delivery and toxicity in GBM chemotherapy, supported by their excellent in vitro targeting, in vivo anti-tumor efficacy, and reduced toxicity profile.
Advancements in Nanomedicine for Precision Management of Lymphoma: Mechanisms, Diagnostics, and Therapeutic Strategies.
Wang R, Zhang Z, Wang Q … +4 more , Gu P, Yang Y, Wang B, Teng Y
Int J Nanomedicine · 2026 · PMID 42046736 · Full text
Lymphoma is a heterogeneous malignancy originating from the lymphatic and hematopoietic systems. Traditional diagnostic and therapeutic approaches face significant limitations due to the complexity, dissemination, and dr...
Lymphoma is a heterogeneous malignancy originating from the lymphatic and hematopoietic systems. Traditional diagnostic and therapeutic approaches face significant limitations due to the complexity, dissemination, and drug resistance associated with lymphoma. Thus, novel approaches are required for precise management and treatment. Recently, advances in nanotechnology have provided new possibilities for lymphoma therapy, particularly through interdisciplinary research combining materials science and biomedicine, thus offering promising strategies for precision treatment. This review systematically summarizes recent advancements in nanomedicine for lymphoma management. First, it introduces mechanisms of nanotechnological interventions, emphasizing lymphoma's pathological features. Next, cutting-edge diagnostic applications, including extracellular vesicle detection, high-sensitivity nucleic acid biomarker sensing, and multimodal imaging, are highlighted. Additionally, emerging therapeutic strategies such as integrated nanoplatforms combining diagnostics, treatment, and real-time monitoring are discussed. Examples include optimized mRNA vaccine delivery, enhanced chimeric antigen receptor (CAR) T-cell therapy, bispecific nanoparticle systems, and combination gene/chemotherapy approaches. Finally, this review outlines the challenges associated with clinical translation and suggests future directions for intelligent adaptive nanomedicine, emphasizing its potential to significantly advance lymphoma diagnosis and therapeutic paradigms.
Quercetin-Based Advanced Delivery Systems - From Multimodal Nano-theranostics to Microneedles: a Recent Update on Their Preclinical Studies.
Beena M, Udduttula A, Palaniappan A
Int J Nanomedicine · 2026 · PMID 42046735 · Full text
Quercetin is a naturally derived flavonoid that has received growing attention for its wide range of pharmacological activities such as strong anticancer, antimicrobial, anti-inflammatory, and antioxidant effects. Its mu...
Quercetin is a naturally derived flavonoid that has received growing attention for its wide range of pharmacological activities such as strong anticancer, antimicrobial, anti-inflammatory, and antioxidant effects. Its multiple functions and natural bioactivity make it an appealing therapeutic candidate. However, the clinical use of quercetin is still limited by issues like poor water solubility, low bioavailability, fast metabolism, and difficulties in achieving targeted delivery. Recent research has aimed to overcome these challenges through innovative formulation strategies like nanoencapsulation, polymeric carriers, 3D printing, microneedle scaffolds and surface modification. These approaches improve stability, boost bioavailability, and allow for targeted therapeutic effects. Traditional theranostic systems that use nanoparticles, quantum dots, or linked biomolecules have enhanced precision medicine by merging diagnostic imaging methods, such as MRI, PET, and fluorescence, with treatment options like targeted drug delivery and photothermal therapy. Yet, these systems face issues related to biocompatibility, cost, biodegradability, and targeting precision. Platforms based on quercetin are emerging as a promising alternative to tackle these problems. Despite their potential, this area is largely uncharted, and, to our knowledge, no thorough review has focused on quercetin's role in multifunctional theranostic systems. This review offers a systematic look at the design strategies, biomedical uses, and potential for quercetin-based theranostics. We discuss key challenges, such as achieving controlled/stimuli-responsive delivery, validation in higher animal studies, scale-up and to emphasize future directions for evolving quercetin-based platforms as next-generation nano-theranostics.
Preclinical Nanoparticle Approaches Targeting Tumor-Associated Macrophages in Breast Cancer: From Mechanisms to Therapeutic Strategies.
Teng J, Zhang X, Shen C … +7 more , Wang L, Hu J, Li Z, Liu Y, Liu J, Wei S, Wang L
Int J Nanomedicine · 2026 · PMID 42046734 · Full text
Breast cancer is the most common malignancy among women worldwide, with high incidence and mortality rates. Tumor-associated macrophages (TAMs) are key mediators in the immunosuppressive tumor microenvironment (TME), con...
Breast cancer is the most common malignancy among women worldwide, with high incidence and mortality rates. Tumor-associated macrophages (TAMs) are key mediators in the immunosuppressive tumor microenvironment (TME), contributing to poor prognosis and reducing immunotherapy efficacy. This review examines the dual roles of TAMs in breast cancer progression. TAMs are known to promote tumor development through angiogenesis, immune evasion, and metastasis, while M1-polarized TAMs conversely enhance antitumor immunity. Herein, the nanoparticle-based strategies targeting TAMs presented in preclinical research are explored, including reprogramming M2 to M1 macrophages, delivering MYC inhibitors, depleting TAMs, and inhibiting TAM recruitment. Integration with immune checkpoint inhibitors is also discussed. Challenges in translating these nanoparticle approaches from preclinical models to clinical practice are further addressed, with an emphasis placed on human-relevant models, optimized production processes, and personalized therapeutic approaches.
Natural Bioactive-Based Advanced Wound Dressings for Diabetic Wound Healing: A Systematic Review of Emerging Biomaterial Platforms.
Fahrurroji A, Suhandi C, Chaerunisaa AY … +2 more , Pratiwi L, Sriwidodo S
Int J Nanomedicine · 2026 · PMID 42039854 · Full text
BACKGROUND: Diabetic ulcers are complex wounds that are difficult to treat due to persistent inflammation, excessive oxidative stress, impaired angiogenesis, and microbial infections that disrupt normal healing. Advanced...
BACKGROUND: Diabetic ulcers are complex wounds that are difficult to treat due to persistent inflammation, excessive oxidative stress, impaired angiogenesis, and microbial infections that disrupt normal healing. Advanced wound dressings such as hydrogels, nanofibre matrices, hydrocolloids, and 3D bioprinted constructs are increasingly developed to incorporate natural bioactive compounds with multifunctional therapeutic properties. However, systematic understanding of their mechanisms and translational relevance remains limited. OBJECTIVE: This study aims to systematically review natural-based hydrogel, hydrocolloid, and hydrofiber formulations in diabetic wound healing. METHODS: A Systematic Literature Review following PRISMA guidelines was conducted using ScienceDirect, SpringerLink, PubMed, and Scopus (2020-2025). Risk of bias was assessed using SYRCLE's tool. RESULTS: From 5256 initial records, 4412 articles were screened, and 14 studies were included after applying eligibility criteria. These studies examined advanced dressings such as hydrogels, hydrocolloids, nanofibers, 3D bioprinted constructs, and hybrid nanocomposites incorporating natural bioactive compounds. The formulations demonstrated antimicrobial, anti-inflammatory, antioxidant, pro-angiogenic, and re-epithelialization effects. Common compounds included curcumin, berberine, propolis, bee venom, and plant extracts combined with polymers such as chitosan, alginate, hyaluronic acid, collagen, and GelMA. Advanced fabrication improved drug delivery, physicochemical properties, and healing outcomes. At the molecular level, these systems modulated pathways such as NF-κB, PI3K/Akt, MAPK, VEGF, and TGF-β/Smad, contributing to reduced inflammation, oxidative stress suppression, enhanced angiogenesis, and extracellular matrix remodeling. Risk of bias assessment indicated unclear risks in randomization and blinding, although internal validity was generally acceptable Translational readiness remained limited (TRL 2-6), with hydrogels and nanosystems showing the highest potential, while 3D bioprinting faces scalability and regulatory challenges. CONCLUSION: Natural-based advanced dressings offer a promising strategy for diabetic wound management. Successful clinical translation requires alignment with scalability, stability, cost-effectiveness, and regulatory compliance. Future research should prioritize standardized preclinical models, controlled release systems, and scalable, regulation-compliant biomaterial designs to accelerate clinical application.
Concept of 2D van der Waals Nanohybrids for Key Biomedical Applications.
Rejinold NS, Choy JH
Int J Nanomedicine · 2026 · PMID 42039853 · Full text
The past decade has witnessed a fundamental shift in 2D nanomaterials, from isolated single-component sheets to vdW nanohybrids, architected as stacked, stitched, or surface-engineered assemblies of chemically distinct l...
The past decade has witnessed a fundamental shift in 2D nanomaterials, from isolated single-component sheets to vdW nanohybrids, architected as stacked, stitched, or surface-engineered assemblies of chemically distinct layers. Enabled by weak interlayer forces, these hybrids permit modular integration of photonic, catalytic, electronic, and bioactive functions without lattice matching or harsh chemistries. In biomedicine, this modularity is transformative: one layer can absorb Near Infrared, NIR light for photothermal or photodynamic therapy, another can intercalate and release drugs or nucleic acids, a third can modulate redox biology through ROS scavenging or nanozyme activity, while polymeric or biomimetic coatings provide immune evasion, targeting, or biodegradability. Compared with isotropic nanoparticles, 2D vdW interfaces offer maximal surface area, multivalent binding, anisotropic ion/electron transport, tissue-compliant mechanics, and engineerable interlayer galleries for controlled, stimulus-responsive release. Crucially, vdW stacking preserves the intrinsic properties of each layer while enabling emergent synergistic behaviors including photothermal-photodynamic coupling, catalytic-photonic amplification, mechanobiology-driven responsiveness, and staged therapeutic logic. Together, these attributes position vdW nanohybrids as a powerful and versatile class of materials poised to redefine therapeutic, diagnostic, regenerative, and bioelectronic frontiers in next-generation nanomedicine.
Synergistic Sono-Chemodynamic Therapy of Renal Cell Carcinoma Using HKUST-1@TiO Heterojunctions.
Zheng S, Li C, Chen J … +4 more , Zhang K, Cui X, Li R, Weng Z
Int J Nanomedicine · 2026 · PMID 42039852 · Full text
INTRODUCTION: Renal cell carcinoma (RCC) is a common urinary malignancy with high postoperative recurrence, and current therapies are limited by toxicity or insufficient efficacy. Efficient sonodynamic therapy (SDT) stra...
INTRODUCTION: Renal cell carcinoma (RCC) is a common urinary malignancy with high postoperative recurrence, and current therapies are limited by toxicity or insufficient efficacy. Efficient sonodynamic therapy (SDT) strategies capable of generating reactive oxygen species (ROS) are urgently needed. This study aimed to develop a high-performance MOF-based heterojunction sonosensitizer to enhance ROS generation and achieve effective anti-tumor activity. METHODS: We synthesized HKUST-1@TiO heterojunctions and characterized their morphology, electronic structure, and ROS generation capacity. In vitro, OSRC-2 cells were treated with HKUST-1@TiO ± ultrasound; cell viability, proliferation, apoptosis, and intracellular ROS were assessed. In vivo, nude mice bearing OSRC-2 xenografts received HKUST-1@TiO ± ultrasound; tumor growth, histopathology, and biosafety markers were analyzed. RESULTS: HKUST-1@TiO exhibited efficient heterojunction formation, which enhanced charge separation and ROS production under ultrasound. In vitro, the combination treatment significantly reduced cell viability, decreased Ki67-positive area, and increased the number of TUNEL-positive cells. Intracellular ROS staining confirmed effective ROS accumulation in tumor cells. In vivo, tumor volume and weight were significantly reduced, with no detectable organ toxicity. CONCLUSION: HKUST-1@TiO heterojunctions effectively augment SDT through enhanced intracellular ROS generation, inducing tumor cell apoptosis and inhibiting proliferation. This study addresses the unmet need for efficient and safe SDT for RCC and provides a promising strategy with translational potential.
Advances in Nano-Drug Delivery Systems for Osteosarcoma: From Targeting Strategies to Combating Lung Metastasis.
Jia S, Gong B, Chen H … +5 more , Chen Y, Zhuo C, Wu H, Qu X, Cai H
Int J Nanomedicine · 2026 · PMID 42039851 · Full text
Osteosarcoma (OS) is the most prevalent primary malignant bone tumor in children and adolescents, characterized by aggressive local invasion, early distant metastasis (predominantly lung metastasis), and poor prognosis....
Osteosarcoma (OS) is the most prevalent primary malignant bone tumor in children and adolescents, characterized by aggressive local invasion, early distant metastasis (predominantly lung metastasis), and poor prognosis. Conventional clinical regimens, mainly neoadjuvant chemotherapy combined with surgical resection, are limited by severe systemic toxicity, multidrug resistance, low tumor targeting, and unsatisfactory outcomes for metastatic OS, with the 5-year survival rate of metastatic patients remaining below 30%. Nanodrug delivery systems (NDDS) have emerged as a transformative strategy to address these bottlenecks by enabling targeted drug/gene delivery, controlled release, enhanced tumor accumulation, and reduced off-target effects. This review systematically summarizes the pathological characteristics and therapeutic dilemmas of OS, highlights recent advances in diverse NDDS including lipid nanoparticles, polymeric nanoparticles, carbon-based nanomaterials, extracellular vesicles, gold nanoparticles, and hydrogels for OS therapy, with a special focus on strategies to counteract lung metastasis. We further discuss the clinical translation challenges of NDDS in OS, especially pediatric-specific concerns, and propose future directions such as stimuli-responsive nanocarriers, biomimetic nanoparticles, combination therapy, and inhalable nanomedicines for pulmonary metastatic lesions. Overall, NDDS hold great promise to revolutionize OS treatment by improving therapeutic efficacy and safety, particularly in overcoming lung metastasis and chemoresistance.
Oxidoreductase-Like Nanozymes: From Biosensing to Molecular Mechanisms in Disease Therapy.
Cao M, Ma J, Yang Y … +4 more , Cheng M, Liu J, Pan Z, Du Z
Int J Nanomedicine · 2026 · PMID 42039850 · Full text
Nanozymes, a class of nanomaterials capable of mimicking the functions of natural enzymes, have garnered significant attention in biomedical fields because of their stable catalytic activity, high efficiency, low cost, a...
Nanozymes, a class of nanomaterials capable of mimicking the functions of natural enzymes, have garnered significant attention in biomedical fields because of their stable catalytic activity, high efficiency, low cost, and tunable enzyme-like properties. In recent years, advances in nanotechnology have led to the development of numerous nanozymes with redoxase-like activities, which have been widely applied in biosensing and disease treatment, demonstrating considerable potential. In this review, we first summarize the redoxase-like activity of nanozymes. From the perspective of redox regulation, we discuss the catalytic mechanisms of nanozymes in biosensing applications, elaborate on the molecular mechanisms involved in tumor therapy, including the induction of apoptosis and ferroptosis, and examine their catalytic pathways in antibacterial and anti-inflammatory treatments. Finally, we also discuss the current limitations and future challenges of nanozymes in biomedical applications, aiming to provide insights for the rational design and clinical translation of next-generation nanozyme-based platforms.
Translational Nanomedicine for Osteoporosis: Bridging Bone Signaling Networks and Targeted Delivery Systems.
Liu J, Shi S, Huang H … +2 more , Wang C, Liu Y
Int J Nanomedicine · 2026 · PMID 42023083 · Full text
Osteoporosis is a complex skeletal disorder characterized by reduced bone mineral density and microarchitectural deterioration, leading to an increased risk of fractures. Conventional pharmacotherapies, such as bisphosph...
Osteoporosis is a complex skeletal disorder characterized by reduced bone mineral density and microarchitectural deterioration, leading to an increased risk of fractures. Conventional pharmacotherapies, such as bisphosphonates and selective estrogen receptor modulators, are constrained by poor bioavailability, lack of targeting specificity, and systemic side effects. Unlike previous reviews that examine signaling pathways and nanocarrier design in isolation, this review presents an integrated mechanistic framework wherein specific therapeutic nodes within key bone remodeling pathways-including Wnt/β-catenin, BMP/Smad, and RANKL/RANK/OPG-inform the rational design of nanodelivery systems. Within this framework, four major classes of nanoplatforms-inorganic nanoparticles, polymeric carriers, liposomal systems, and biomimetic vesicles-are systematically evaluated for their ability to engage pathway-specific targets and modulate osteogenesis and osteoclastogenesis. In addition to mechanistic efficacy, each platform is critically assessed for clinical translatability using a multi-dimensional benchmarking approach that encompasses in vivo performance, targeting precision, safety profile, manufacturability, and regulatory readiness. While these nanosystems exhibit significant potential to enhance therapeutic precision, controlled drug release, and safety, challenges such as long-term biosafety, immune interactions, and scalable manufacturing continue to pose barriers to clinical implementation. By integrating mechanistic targeting with translational benchmarking, this review provides a stage-stratified translational roadmap to guide the development of intelligent and clinically translatable nanomedicine strategies for osteoporosis.
Clinical Applications and Future Prospects of Metallic Nanoparticles in Diagnosis and Therapy.
Galarza-Arévalo GE, González MP, Romero MP
Int J Nanomedicine · 2026 · PMID 42023082 · Full text
Metallic nanoparticles (MNPs) have emerged as versatile platforms for addressing unmet clinical needs in diagnosis, therapy, and theranostics. This review synthesizes recent advances in the clinical application of iron-,...
Metallic nanoparticles (MNPs) have emerged as versatile platforms for addressing unmet clinical needs in diagnosis, therapy, and theranostics. This review synthesizes recent advances in the clinical application of iron-, gold-, hafnium-, gadolinium-, silver-, copper-, titanium-, and zinc-based nanoparticles across oncology, infection control, biomedical coatings, and diagnostic imaging. In oncology, superparamagnetic iron oxide nanoparticles (SPIONs) have demonstrated a median overall survival of 13.4 months in patients with recurrent glioblastoma and achieved intratumoral temperatures of 42-48.5 °C during magnetic hyperthermia. Gold-silica nano shells generated tumor-free ablation zones in up to 87.5% of prostate lesions, with oncologic success reported in 73% of treated patients. CYT-6091, a ~27 nm PEGylated gold nanoparticle conjugated with TNF-α, enabled systemic delivery of this cytokine without inducing severe hypotension, showing a substantially improved safety profile compared with free TNF-α. In antimicrobial applications, Nano Silver Fluoride reduced dentin caries progression by more than 30% compared with controls, while copper nanoparticle-reinforced universal adhesives preserved mechanical performance and retention rates over 48 months. Collectively, these findings highlight the capacity of MNPs to integrate diagnostic and therapeutic functions, including MRI/CT contrast enhancement, magnetic hyperthermia, photothermal and photodynamic therapies, and gene delivery. Despite significant progress, challenges related to heterogeneous biodistribution, long-term toxicity, and regulatory approval remain, emphasizing the need for the development of safer and more efficient metallic nanomedicines aligned with emerging clinical demands in personalized medicine.
How Transformative Are ROS Responsive Hydrogel Nanoformulations to Treat Refractory Infected Wounds.
Liu Z, Xiang H, Xian K … +3 more , Cai L, Yin D, Zhong J
Int J Nanomedicine · 2026 · PMID 42023081 · Full text
Controlling infection in bacterial-infected wounds presents a formidable challenge, especially when compounded by additional high-risk factors that hinder the healing process during clinical interventions. Currently, the...
Controlling infection in bacterial-infected wounds presents a formidable challenge, especially when compounded by additional high-risk factors that hinder the healing process during clinical interventions. Currently, the efficacy of standard therapeutic approaches often falls short, largely attributed to persistent local infections and inflammatory responses that impede healing cascades. In recent years, increasing reports on the management of hard-to-heal infected wounds have highlighted the potential of reactive oxygen species (ROS)-responsive hydrogels to facilitate wound recovery. The capacity of these hydrogels could be greatly enhanced by integrating them with traditional treatments, thereby addressing the complexities of healing in refractory infected wounds. Therefore, based on a thorough review of latest literatures, this paper comprehensively outlines the molecular mechanisms associated with hard-to-heal infected wounds, the role of ROS-responsive hydrogels in promoting healing, and a combined therapeutic strategy for wound control. It is designed to offer valuable insights to inform and advance future investigative efforts in this research field.
Calcium Carbonate-Stabilized Nano-Caffeine Emulsion Attenuates Diabetic Cardiomyopathy via Antioxidant, Anti-Inflammatory, and Anti-Fibrotic Pathways in Type 2 Diabetic Rats with HPLC-Quantified Cardiac Caffeine Levels.
Mansouri RA, Aboubakr EM, Alshaibi HF … +5 more , Fouda WM, Banjabi AA, Al-Bazi MM, Mohammed HA, Ahmed AM
Int J Nanomedicine · 2026 · PMID 42023080 · Full text
INTRODUCTION: Type 2 diabetes mellitus (T2DM) is one of the most commonly diagnosed metabolic diseases. Notably, two-thirds of diabetic patients may develop diabetic cardiomyopathy (DCM), a life-threatening condition for...
INTRODUCTION: Type 2 diabetes mellitus (T2DM) is one of the most commonly diagnosed metabolic diseases. Notably, two-thirds of diabetic patients may develop diabetic cardiomyopathy (DCM), a life-threatening condition for which no curative treatment currently exists. METHODS: This study aimed to investigate the potential ameliorative effects of caffeine against DCM development, utilizing a novel oral sustained-release caffeine-loaded Pickering emulsion formula stabilized by calcium carbonate nanoparticles to enhance its pharmaceutical and pharmacological properties. Eighty-four rats were divided into seven groups: control, caffeine, nano-caffeine, diabetic, diabetic + rosuvastatin, diabetic + caffeine, and diabetic + nano-caffeine. RESULTS: Our findings demonstrated that the newly developed nano-caffeine formulation significantly downregulated myocardial injury markers (CK-MB, cTnI, ALT, AST, and LDH) and markedly ameliorated myocardial tissue injury and fibrosis, as confirmed by histopathological examination and desmin/α-SMA expression analysis. Additionally, the nano-caffeine treatment reduced inflammatory cytokines (TNF-α and IL-1β), attenuated hyperlipidemia, decreased iNOS and NO myocardial concentrations, and upregulated protective antioxidants (Nrf2, GSH, GSH-Px, SOD, and catalase) compared to the control group. Importantly, the cardioprotective effects of nano-caffeine were more pronounced than those observed in caffeine-treated diabetic rats. Furthermore, a novel, simple, and validated HPLC method was employed to quantify caffeine levels in cardiac tissues in all groups. The analysis revealed significantly higher caffeine concentrations in the nano-caffeine group compared to other groups, indicating improved tissue delivery. CONCLUSION: The formulation significantly enhances the cardioprotective effects of caffeine against myocardial injury in T2DM rats by optimizing its pharmacodynamic and pharmacokinetic properties.
Nanomedicine for Cardiac Repair in Heart Failure: From Targeted Delivery to Regenerative Modulation.
Wang W, Wang Q
Int J Nanomedicine · 2026 · PMID 42016346 · Full text
Heart failure is a progressive syndrome in which the heart fails to maintain adequate output and remains a leading cause of mortality and healthcare utilization despite guideline-directed pharmacological and device-based...
Heart failure is a progressive syndrome in which the heart fails to maintain adequate output and remains a leading cause of mortality and healthcare utilization despite guideline-directed pharmacological and device-based therapies. A major contributor to this residual burden is the limited myocardial specificity of conventional treatments, which act systemically and incompletely address the heterogeneous microenvironment of the failing ventricle. Nanomedicine employs nanoscale carriers to reshape pharmacokinetics, protect labile cargo, and enhance delivery to injured myocardium. Preclinical studies in predominantly heart failure with reduced ejection fraction (HFrEF) models, including post-myocardial infarction and pressure-overload injury, demonstrate that targeted nanoplatforms can improve left ventricular ejection fraction by approximately 5-15 percentage points, reduce infarct size by 20-50%, and attenuate fibrosis, inflammation, or cardiomyocyte apoptosis by 30-60% compared with control treatments. Spatially and temporally controlled delivery of small molecules, proteins, and nucleic acids is possible using organic and inorganic nanoparticles and catalytic systems, biomimetic and bioderived carriers, extracellular vesicles, and nanostructured hydrogels or patches, with some also providing mechanical support or theranostic imaging. There is limited evidence in heart failure with preserved ejection fraction (HFpEF). Early studies have focused on inflammation, fibrosis, and microvascular dysfunction rather than on contractile recovery. Importantly, the majority of nanomedicine strategies discussed remain at the preclinical stage, with clinical experience largely confined to early-phase safety and feasibility studies. This review summarizes information from in vitro systems, small- and large-animal models, and newly developed clinical studies, and critically examines translational issues such as toxicity, immunogenicity, scalability, and regulatory complexity. New approaches to cardiac regeneration, such as local delivery of pro-regenerative signals, are also supported by nanomedicine, which facilitates the delivery of pro-regenerative cues, such as regulatory RNAs and extracellular vesicles, to promote cardiomyocyte survival, angiogenesis, and limited myocardial tissue renewal.
Layered Double Hydroxide-Loaded Dl-3-n-Butylphthalide Alleviates Renal Ischemia-Reperfusion Injury by Regulating the PI3K-AKT-Nrf2 Signaling Pathway.
Yan Y, Wang K, Ren L … +11 more , Ma JJ, Zhu XC, Ding HF, Chu JX, Zhu ZG, Xia JY, Xia Y, Xu Y, He MH, Wang WR, Zhang CL
Int J Nanomedicine · 2026 · PMID 42016345 · Full text
PURPOSE: This study aims to address the issues that limit the clinical application of Dl-3-n-butylphthalide (NBP) due to its poor water solubility and low bioavailability, and to explore its therapeutic potential in rena...
PURPOSE: This study aims to address the issues that limit the clinical application of Dl-3-n-butylphthalide (NBP) due to its poor water solubility and low bioavailability, and to explore its therapeutic potential in renal ischemia-reperfusion (I/R) injury. We attempted to utilize layered double hydroxide (LDH) to construct a novel nano-drug delivery system to enhance the stability and efficacy of NBP, and to deeply investigate its potential mechanism of action. METHODS: By loading NBP onto LDH, LDHs-NBP nanocomplexes were successfully constructed. Subsequently, the effects of LDHs-NBP on renal function, tissue pathology, cell apoptosis, oxidative stress and mitochondrial function were systematically evaluated in rat renal ischemia-reperfusion injury models and HK-2 cell hypoxia/reoxygenation models. The molecular mechanism of the PI3K-AKT-Nrf2 signaling pathway was analyzed through immunohistochemistry and Western Blot. RESULTS: The experimental results show that the drug loading capacity of LDHs-NBP nanocomplexes is 24.26%. Compared with pure NBP, LDHs-NBP more effectively improve renal function in rats, reduces serum creatinine (SCr) and blood urea nitrogen (BUN), decreases inflammatory infiltration and structural damage in renal tissues, and exhibits stronger antioxidant capacity-evidenced by decreased malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities. At the cellular level, LDHs-NBP significantly inhibits apoptosis and ROS production in HK-2 cells, alleviates mitochondrial dysfunction, and its protective effect is closely associated with activation of the PI3K-AKT-Nrf2 signaling pathway. CONCLUSION: This study successfully constructed an NBP nano-complex based on LDH, and confirmed that LDHs-NBP has significant therapeutic advantages in renal ischemia-reperfusion injury. The mechanism may be related to the activation of the PI3K-AKT-Nrf2 pathway. This study provides experimental evidence for the application of LDHs-NBP in the treatment of renal ischemia-reperfusion injury, and shows a promising translational prospect and clinical value.
Nanomedicine-Integrated Phototherapy for Cancer Theranostics: A Systematic Review of Photoresponsive Materials, Mechanisms, and Clinical Translation.
Alsaikhan F, Al-Saikhan TF, Alsaikhan YF
Int J Nanomedicine · 2026 · PMID 42016344 · Full text
BACKGROUND: Cancer remains a principal cause of mortality worldwide, and conventional treatments are constrained by non-specific cytotoxicity, therapeutic resistance, and incomplete tumor eradication. Nanomedicine-integr...
BACKGROUND: Cancer remains a principal cause of mortality worldwide, and conventional treatments are constrained by non-specific cytotoxicity, therapeutic resistance, and incomplete tumor eradication. Nanomedicine-integrated phototherapy, encompassing photodynamic therapy (PDT) and photothermal therapy (PTT), has emerged as a spatiotemporally controlled theranostic modality with demonstrated preclinical promise. OBJECTIVE: This systematic review synthesizes current evidence on nanomedicine-based phototherapeutic agents across four research dimensions: nanotechnology design, phototherapeutic mechanisms, photoresponsive materials, and clinical translation. METHODS: A systematic literature search was conducted across PubMed, Scopus, Web of Science, and Embase (2000-2024) using predefined search terms related to nanomedicine, PDT, PTT, and cancer theranostics. Studies were screened according to PRISMA-aligned inclusion and exclusion criteria. A total of 1847 records were identified; following deduplication and full-text review, 78 studies met eligibility criteria and were included in the narrative synthesis. RESULTS: Nanocarrier design has advanced substantially, with enhanced permeability and retention (EPR)-mediated and active-targeted platforms achieving 10-50-fold tumor-to-tissue concentration ratios in preclinical models. Photoresponsive nanomaterials (including gold nanostructures with PCE 50-99%, carbon-based nanomaterials with PCE 40-80%, and hybrid metal-organic frameworks) demonstrate tunable optical properties suitable for NIR-activated therapy. Multifunctional theranostic platforms combining PDT or PTT with chemotherapy, immunotherapy, and multimodal imaging show synergistic efficacy. Clinical translation remains limited, with gold nanoshells (AuroLase Therapy, Nanospectra Biosciences) in Phase I evaluation for prostate cancer and several PDT photosensitizer formulations carrying regulatory approval. CONCLUSION: Nanomedicine-integrated phototherapy addresses fundamental limitations of conventional oncology. Realizing its clinical potential requires development of biodegradable nanocarriers, standardized characterization protocols, companion diagnostics for patient stratification, and coordinated regulatory pathways. EPR variability in human tumors and the predominance of preclinical data necessitate a calibrated assessment of translational feasibility.
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