International Journal Of Nanomedicine[JOURNAL]
Sun
200 papers
Development and Evaluation of Liposomal Nanobiotics for Combating Antibiotic Resistance Among Enterobacteriaceae.
Devi T B, K V DF, Kini S … +1 more , Deekshit VK
Int J Nanomedicine · 2026 · PMID 42333284 · Full text
BACKGROUND: The increasing prevalence of antimicrobial-resistant bacteria, such as , and non-typhoidal , poses a significant healthcare problem, leading to increased mortality. Liposomal nanocarriers have already shown t...
BACKGROUND: The increasing prevalence of antimicrobial-resistant bacteria, such as , and non-typhoidal , poses a significant healthcare problem, leading to increased mortality. Liposomal nanocarriers have already shown their potential in overcoming resistance and improving antibiotic delivery. METHODS: In this study, liposome-based nanocarriers encapsulating conventional antibiotics were developed, characterised and evaluated for their antibacterial efficacy and interactions with bacteria. The liposomal nanobiotics were prepared using the thin-film hydration method and loaded with antibiotics. RESULTS: The prepared nanobiotics of tetracycline, chloramphenicol and nalidixic acid showed average particle size of 120-190 nm and entrapment ranging between 30% and 85% for the antibiotics used. Furthermore, the formulations exhibited minimal cytotoxic effects on HEK293 cells, indicating favourable biocompatibility. Compared to the free antibiotics the nanobiotics demonstrated significantly enhanced antibacterial activity against MDR isolates. The time kill curves showed significant reduction in viable bacterial count, while in vitro release profile showed sustained release of the encapsulated liposomes around 85% within 24 hours. The TEM analysis and PI/calceinAM assay demonstrated effective liposme-bacterial interaction and enhanced intracellular delivery of the encapsulated antibiotics. Further, the analysis of the efflux-pump associated genes showed impact of nanobiotic formulations on efflux pump gene expressions and suggests a role in mitigating the resistance mechanism. Also, antibiotics encapsulated in liposomes significantly reduced the bacterial load across all conditions in the food-spiking experiment with enhanced antibiotic delivery. CONCLUSION: The liposomal formulation of tetracycline, chloramphenicol and nalidixic acid showed better physicochemical properties, sustained release profile and increased antibacterial activity against MDR bacterial isolates compared to free drug. Overall findings suggest that encapsulation enhances the therapeutic potential of the conventional antibiotics and can be a promising strategy to overcome the multi-drug resistance in bacteria.
Nano-Immunotherapy Targeting TAMs: Precisely Regulating TAMs to Reverse Immunosuppressive TME.
Zhang JM, Dong CL, Li B
Int J Nanomedicine · 2026 · PMID 42333283 · Full text
Given the crucial role of tumor-associated macrophages (TAMs) in cancer development, nano-immunotherapy targeting TAMs represents a pivotal strategy for reversing the immunosuppressive tumor microenvironment (TME) and in...
Given the crucial role of tumor-associated macrophages (TAMs) in cancer development, nano-immunotherapy targeting TAMs represents a pivotal strategy for reversing the immunosuppressive tumor microenvironment (TME) and inhibiting cancer progression. Nano-drug delivery systems have evolved into multimodal platforms that utilize multi-drug synergy and integrated physical energy interventions, showing considerable potential for enhancing drug targeting and biocompatibility. The core objective of TAM-targeted nano-immunotherapy lies in the precise regulation and functional remodeling of TAMs, as well as the synergistic reversal of the immunosuppressive TME. This review addresses the knowledge gaps and challenges in nano-immunotherapy targeting TAMs and explores recent advances in TAM-targeted immunotherapy using various strategies and nanocarriers, with particular emphasis on the relevant cell surface receptors and downstream signaling pathways. Nano-immunotherapeutic strategies targeting TAMs include reprogramming TAMs, influencing TAM polarization, regulating TAM-secreted mediators, inducing TAM exhaustion, enhancing TAM phagocytosis, modulating TAM metabolism, inhibiting TAM recruitment, and blocking PD-L1 expression on TAMs. The innovations of nanocarriers involve the entire chain intelligent design from inorganic nanocrystals, organic polymers to organic-inorganic hybrid systems, and the precise "Trojan horses" constructed using biodegradable polymers and biomimetic membrane vesicles. Intelligent nanorobots targeting TAMs, as autonomous diagnostic and therapeutic systems integrating sensing, decision-making, and execution, represent an effective approach to enhancing the precision and intelligence of anti-tumor strategies.
Nanomedicine Strategies for Rheumatoid Arthritis: Precision Delivery and Immune Microenvironment Modulation.
He Q, Xing J, Kang J … +3 more , Yang Y, Ma D, Zhang L
Int J Nanomedicine · 2026 · PMID 42325403 · Full text
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation, pannus formation, and progressive joint destruction. Despite their established clinical benefits, conventional antirheuma...
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation, pannus formation, and progressive joint destruction. Despite their established clinical benefits, conventional antirheumatic drugs remain hampered by poor targeting precision, systemic toxicity, and inadequate immunomodulation of the dysregulated microenvironment. The recent development of nanomedicine technology offers transformative potential to address these therapeutic challenges. This review comprehensively examines the application of advanced nano-platforms in RA management, with particular focus on their dual roles in precision drug delivery and immune microenvironment remodeling. The discussion encompasses multifunctional nanomaterials that enable precise drug transport while actively regulating pathological processes through reactive oxygen species scavenging, hypoxia mitigation, and immune cell reprogramming. Additionally, the integration of diagnostic and therapeutic functions within nanomaterial systems represents a significant advancement in RA theranostics. Finally, translational challenges and future directions are critically analyzed to map the clinical development path for intelligent RA nanomedicine.
Size-Dependent Layered Double Hydroxide Nanoparticles Promote Osteogenesis and Bone Regeneration via METTL3-Dependent N6-Methyladenosine Modification of Runx2 mRNA.
Zhu Y, Sun W, Huang Y … +5 more , Li J, Jiang H, Luo C, Wan F, Zhou Z
Int J Nanomedicine · 2026 · PMID 42325402 · Full text
BACKGROUND: The osteogenic efficacy of mesenchymal stem cell (MSC)-based bone regeneration is often limited by insufficient osteogenic differentiation. Layered double hydroxide (LDH) nanoparticles are promising biomateri...
BACKGROUND: The osteogenic efficacy of mesenchymal stem cell (MSC)-based bone regeneration is often limited by insufficient osteogenic differentiation. Layered double hydroxide (LDH) nanoparticles are promising biomaterials, but whether their intrinsic osteoinductive activity is regulated by particle size and epitranscriptomic mechanisms remains unclear. This study investigated whether LDH nanoparticles promote osteogenesis in bone marrow-derived MSCs (BMSCs) through METTL3-dependent N6-methyladenosine (m6A) modification. METHODS: BMSCs were treated with 50 nm or 100 nm LDH nanoparticles under osteogenic induction. Osteogenic differentiation was evaluated by alkaline phosphatase activity, mineralization staining, osteogenic gene/protein expression, and cytoskeletal morphology. Global m6A levels and m6A regulator expression were assessed, and the role of METTL3 was examined using Mettl3 knockdown. Runx2 mRNA m6A enrichment and stability were analyzed by MeRIP-qPCR and actinomycin D chase assays. Bone regeneration was further evaluated using a GelMA-LDH hydrogel in a murine calvarial defect model. RESULTS: LDH nanoparticles promoted BMSC osteogenesis in a size-dependent manner, with 100 nm LDH producing stronger ALP activity, mineralization, and osteogenic marker expression than 50 nm LDH. Mechanistically, 100 nm LDH increased global m6A methylation and selectively upregulated METTL3. Mettl3 knockdown markedly impaired osteogenesis and abolished the pro-osteogenic effects of LDH. LDH enhanced m6A modification of Runx2 mRNA and prolonged Runx2 transcript stability, thereby supporting RUNX2-mediated osteogenic programming. In vivo, GelMA-LDH implantation significantly enhanced calvarial bone repair and increased RUNX2 and METTL3 expression within defect regions. CONCLUSION: Among the two tested particle sizes, 100 nm LDH nanoparticles exhibited superior pro-osteogenic activity and promoted bone regeneration through a METTL3-dependent m6A mechanism that stabilizes Runx2 mRNA.
How PLGA Microspheres are Emerging as a Key Drug Delivery System.
Qian S, Ma L, Liu C … +3 more , Lin Y, Wu J, Wang X
Int J Nanomedicine · 2026 · PMID 42325401 · Full text
Poly(lactic-co-glycolic acid) (PLGA) microspheres are a clinically established platform for sustained and controlled drug delivery, offering tunable degradation and reduced dosing frequency. This review critically apprai...
Poly(lactic-co-glycolic acid) (PLGA) microspheres are a clinically established platform for sustained and controlled drug delivery, offering tunable degradation and reduced dosing frequency. This review critically appraises PLGA microsphere technology, linking materials science with clinical translation. We examine how molecular parameters-molecular weight, lactide-to-glycolide ratio, and terminal group chemistry-affect degradation and release kinetics. Key fabrication methods (emulsion-solvent evaporation, spray drying, membrane emulsification, and microfluidics) are compared for their control over encapsulation efficiency, particle size, and scalability. Release mechanisms, including diffusion, swelling, and erosion, are discussed alongside strategies to mitigate burst release. The review also addresses in vivo pharmacokinetics, recent clinical progress in oncology and vaccine delivery, regulatory challenges, manufacturing hurdles, and future directions such as stimuli-responsive microspheres and AI-guided formulation design.
cGAMP-Loaded M2e Nanovaccine Elicits Cross-Reactive Immunity and Mitigates H6N1 Avian Influenza Infection in Chickens.
Chen LY, Tsai HH, Peng L … +4 more , Yao BY, Chiu J, Hu CJ, Chen HW
Int J Nanomedicine · 2026 · PMID 42325400 · Full text
INTRODUCTION: Avian influenza virus (AIV) is a rapidly evolving zoonotic pathogen that causes significant economic loss in the poultry industry and threatens public health. In the development of a broadly protective infl...
INTRODUCTION: Avian influenza virus (AIV) is a rapidly evolving zoonotic pathogen that causes significant economic loss in the poultry industry and threatens public health. In the development of a broadly protective influenza vaccine, the extracellular domain of matrix protein 2 (M2e) is a promising antigen candidate as it is highly conserved across most influenza A subtypes. M2e-induced immune protection is primarily mediated through antibody-dependent cellular cytotoxicity (ADCC), which enables the clearance of infected cells before viral release. However, the immunogenicity of M2e is limited due to its small size and low abundance on the viral surface, necessitating effective antigen delivery systems to enhance its presentation. METHODS: We developed a PLGA-based nanoshell vaccine co-encapsulating M2e peptide and a STING agonist and evaluated its immunogenicity and protective efficacy in specific-pathogen-free (SPF) chickens. RESULTS: Immunization of SPF chickens with the M2e nanoshell vaccine significantly enhanced immune-related gene expression and B-cell expansion, leading to a robust and durable M2e-specific antibody response. In addition, the induced antibodies demonstrated cross-reactivity by effectively recognizing the M2e protein expressed on MDCK cells infected with seven different strains of influenza viruses. Following H6N1 challenge, vaccinated chickens showed attenuated lesions in the kidneys and decreased viral load and viral antigen in the respiratory and intestinal lymphoid tissues, suggesting reduced viral replication. Furthermore, to explore potential Fc-mediated effector functions, an in vitro killing assay demonstrated that chicken splenic natural killer cells were capable of lysing influenza-infected target cells in the presence of serum from M2e nanoshell-immunized chickens, providing initial functional evidence of ADCC activity in the avian system. CONCLUSION: Collectively, these results demonstrate that the M2e nanoshell vaccine elicits durable and cross-reactive immune responses and reduces tissue damage, potentially involving ADCC-mediated effector mechanisms. The M2e nanoshell vaccine shows potential as a broadly protective avian influenza vaccine and holds value for controlling AIV outbreaks in poultry.
Application of Cerium-Tannic Acid-Formaldehyde Coordination Polymer Colloidal Nanomaterials to Alleviate Lipopolysaccharide-Induced Acute Lung Injury.
Wu X, Xue F, Cheng D … +13 more , Hong L, Li C, Ni M, Liang S, Chen T, Luo C, Ren J, Wu K, Liu T, Zhang J, Wei J, Liu C, Wu Q
Int J Nanomedicine · 2026 · PMID 42325399 · Full text
BACKGROUND: Acute lung injury (ALI) is a severe respiratory disease worldwide and is characterized by a high mortality rate. Effective therapeutic interventions remain limited. Although metal-polyphenol coordination poly...
BACKGROUND: Acute lung injury (ALI) is a severe respiratory disease worldwide and is characterized by a high mortality rate. Effective therapeutic interventions remain limited. Although metal-polyphenol coordination polymers (MPCPs) have shown considerable therapeutic potential across diverse pathological conditions, their application in ALI, along with the elucidation of the molecular mechanisms, remains insufficiently explored. METHODS: Based on the coordination interaction between cerium (Ce) and tannic acid (TA), a Ce-TA nanomaterial was synthesized through a facile and cost-effective method. The properties, stability, radical scavenging activity, and enzyme-like activity of Ce-TA were evaluated. Comprehensive assessments of its therapeutic effects and biosafety were performed using various cell models and a lipopolysaccharide (LPS)-induced ALI mouse model. RESULTS: Ce-TA exhibited ultrasmall size and high colloidal stability, efficiently scavenging multiple free radicals via its superoxide dismutase (SOD)-like and catalase (CAT)-like enzyme activities. Ce-TA inhibited HO-induced apoptosis and ROS production in BEAS-2B cells and human umbilical vein endothelial cells (HUVECs). Compared with the LPS group, Ce-TA effectively alleviated LPS-induced ALI by ameliorating lung histopathological injury, decreasing lung wet/dry weight (W/D) ratio, myeloperoxidase (MPO) and malondialdehyde (MDA) levels, and reducing inflammatory cytokine levels in vivo via activation of the PI3K/AKT/Nrf2 signaling pathway. CONCLUSION: Ce-TA demonstrated significant anti-inflammatory and antioxidant effects both in vivo and in vitro, with confirmed safety for long-term application. It alleviated LPS-induced ALI by activating the PI3K/AKT/Nrf2 signaling pathway. The facile and economical synthesis of Ce-TA highlights its potential for clinical application, and these advantages make it a promising therapeutic agent for ALI.
Astragaloside IV Co-Loaded Osimertinib Liposomes Alleviate EGFR-TKI Resistance in Non-Small Cell Lung Cancer.
Li M, Tang Y, He Y … +4 more , Xie CY, Zhang JR, Gong Z, Zhang LL
Int J Nanomedicine · 2026 · PMID 42325398 · Full text
INTRODUCTION: Advances in tumor biology have established EGFR-tyrosine kinase inhibitors (EGFR-TKIs) as a key therapy for non-small cell lung cancer (NSCLC). Osimertinib (OSI), a third-generation EGFR-TKI, however, often...
INTRODUCTION: Advances in tumor biology have established EGFR-tyrosine kinase inhibitors (EGFR-TKIs) as a key therapy for non-small cell lung cancer (NSCLC). Osimertinib (OSI), a third-generation EGFR-TKI, however, often leads to acquired resistance within about a year. Astragaloside IV (AS-IV), a bioactive saponin from Astragalus membranaceus, exhibits anti-tumor potential and may help reverse resistance-related epithelial-mesenchymal transition (EMT), a process mediated by TGF-β. While combining OSI with AS-IV is a promising strategy, its efficacy is limited by poor solubility and toxicity-challenges that can be addressed through liposomal co-delivery. METHODS: We prepared OSI and AS-IV co-loaded liposomes (LPs-OSI/AS) and characterized their physicochemical properties and drug release in vitro. Cellular uptake and anti-proliferative effects were evaluated in OSI-sensitive (NCI-H1975) and OSI-resistant (NCI-H1975/AR) NSCLC cells. EMT-related gene expression was analyzed by RT-qPCR. In vivo efficacy was assessed using a subcutaneous xenograft model in BALB/c-nu mice by monitoring tumor growth and body weight. RESULTS: LPs-OSI/AS liposomes were successfully prepared with uniform particle size (96.92 ± 12.04 nm, PDI 0.28 ± 0.01), high encapsulation efficiency (AS: 89.74 ± 6.53%; OSI: 84.35 ± 8.82%), and sustained release. In vitro, LPs-OSI/AS significantly inhibited proliferation of both NCI-H1975 and OSI-resistant NCI-H1975/OSIR cells, outperforming free drug controls without obvious cytotoxicity, and downregulated EMT-related genes (). In vivo, LPs-OSI/AS (20 mg/kg OSI + 40 mg/kg AS) reduced tumor volume by approximately 70% compared to OSI monotherapy, with 100% survival and no significant body weight loss. The Ki-67 positive rate was substantially lower in the LPs-OSI/AS group (1.06%) than in the OSI monotherapy group (5.98%), and H&E staining confirmed superior pathological improvement. Safety evaluation demonstrated normal organ structures with no inflammation or necrosis. CONCLUSION: In summary, LPs-OSI/AS effectively inhibits tumor growth by regulating EMT, exhibits favorable biosafety, and represents a promising therapeutic strategy for NSCLC.
Emerging Nanoplatforms are Effective Against Tumor Hypoxia.
Yu Z, Shang Y, He W … +2 more , Xia X, Zhou L
Int J Nanomedicine · 2026 · PMID 42325397 · Full text
Hypoxia is a characteristic feature of the solid tumor microenvironment and serves as a pivotal factor in tumor progression, metastasis, and therapeutic resistance. It has long been recognized as a significant barrier to...
Hypoxia is a characteristic feature of the solid tumor microenvironment and serves as a pivotal factor in tumor progression, metastasis, and therapeutic resistance. It has long been recognized as a significant barrier to advancing cancer therapy. Although traditional oxygen supplementation strategies can partially enhance local oxygen levels, their effectiveness is limited by the spatiotemporal heterogeneity of tumor tissues, low delivery efficiency, and biosafety concerns, making them inadequate for the precise oxygen regulation required by the complex tumor microenvironment. In recent years, nanotechnology-based platforms designed to alleviate hypoxia have emerged as innovative approaches for remodeling the tumor microenvironment and enhancing multimodal synergistic therapies. These platforms operate through three primary strategies: exogenous oxygen delivery, endogenous oxygen generation, and metabolic oxygen conservation. This review systematically elucidates the underlying mechanisms of tumor hypoxia, summarizes the design principles and recent advancements of related nanomedicines, and discusses the potential and challenges of these platforms in multimodal combination therapies. The study aims to furnish a comprehensive reference for the design of hypoxia-alleviating nanoplatforms and the optimization of synergistic therapeutic strategies, with the objective of providing novel insights and prospects for the development of nanomaterials in this domain.
Exosomes in Ovarian Cancer: Promoters, Biomarkers, and Therapeutic Targets.
Wang F, Dong H, Song Y … +1 more , Zhang Y
Int J Nanomedicine · 2026 · PMID 42325396 · Full text
Ovarian cancer is an aggressive malignancy treated primarily with surgery and platinum-based chemotherapy. The high recurrence rate and platinum resistance are the primary reasons for poor prognosis in ovarian cancer. Ea...
Ovarian cancer is an aggressive malignancy treated primarily with surgery and platinum-based chemotherapy. The high recurrence rate and platinum resistance are the primary reasons for poor prognosis in ovarian cancer. Early screening can improve patient survival, but there are currently no high-precision biomarkers available. Exosomes are nanoscale vesicles that mediate intercellular communication by transferring bioactive molecules, and their composition reflects pathological states. Late diagnosis is the primary cause of poor prognosis in patients with ovarian cancer. Owing to the high stability conferred by their unique structure, exosomes can serve as an efficient, non-invasive approach for early screening. In the context of drug delivery, engineered exosomes using novel advanced technologies can enhance the specificity of clinical pharmacotherapy and reduce adverse toxic reactions. This review summarizes the latest research findings on ovarian cancer-related exosomes and introduces their important roles in exploring the mechanisms of ovarian cancer progression, metastasis, and chemoresistance, as well as their potential as prognostic biomarkers and therapeutic targets.
The Application of Nanomaterials in Kidney Stone Disease: Emerging Strategies for Early Diagnosis, Targeted Therapy, and Prevention.
Zuo J, Zhang Z, Chen J … +13 more , Gou K, Zhou J, Wen L, Wei H, Li X, Zhan P, Chen P, Li H, Zhao J, Wang H, Fu S, Chen J, Wang J
Int J Nanomedicine · 2026 · PMID 42325395 · Full text
Kidney stone disease is one of the most common urologic disorders worldwide and imposes a growing clinical and socioeconomic burden because of its rising prevalence, high recurrence rate, and association with chronic kid...
Kidney stone disease is one of the most common urologic disorders worldwide and imposes a growing clinical and socioeconomic burden because of its rising prevalence, high recurrence rate, and association with chronic kidney injury and systemic metabolic abnormalities. Calcium oxalate (CaOx) stones remain the predominant stone type, and their formation is now recognized as a multistep process involving urinary supersaturation, crystal nucleation and growth, tubular epithelial injury, oxidative stress, inflammation, and crystal retention. Although current management strategies, including dietary modification, pharmacologic prevention, and endourologic interventions, have substantially improved stone clearance, important limitations remain. These include inadequate early detection, suboptimal prevention of recurrence, insufficient targeting of the local renal microenvironment, and procedure-related complications. Recent advances in nanotechnology offer new opportunities to address these unmet needs. Owing to their large specific surface area, tunable physicochemical properties, versatile surface functionalization, and capacity for multimodal integration, nanomaterials have shown considerable promise in metabolic sensing, urinary biomarker detection, targeted drug delivery, modulation of crystal growth, biomimetic renal targeting, and photothermal or photoresponsive lithotripsy. In parallel, the convergence of nanotechnology with artificial intelligence, smart diagnostic devices, and personalized metabolic profiling is reshaping kidney stone management. This shift is moving the field from passive stone removal toward active risk prediction, dynamic monitoring, and precision prevention. In this review, we summarize recent advances in nanomaterial-based strategies for the diagnosis, treatment, and prevention of kidney stones, with particular emphasis on CaOx disease. We also discuss the major translational barriers, including biocompatibility, long-term safety, regulatory complexity, scalable manufacturing, and cost-effectiveness, and outline future directions for clinically integrated, intelligent, and individualized stone care.
Nanobioconjugate Trispecific Antibody Augments Antitumor Immunity of Triple Negative Breast Cancer.
Chang Q, Liu L
Int J Nanomedicine · 2026 · PMID 42311427 · Full text
INTRODUCTION: Triple-negative breast cancer (TNBC) is characterized as the most unfavorable prognosis of the breast cancer subtype. Chemotherapy is currently the primary treatment owing to a persistent lack of effective...
INTRODUCTION: Triple-negative breast cancer (TNBC) is characterized as the most unfavorable prognosis of the breast cancer subtype. Chemotherapy is currently the primary treatment owing to a persistent lack of effective alternative medicine. To fulfill this unaddressed clinical requirement, we utilized the PGLU-Fc-III-4C MsAb platform to develop a nanobioconjugate trispecific antibody (TsAb; CD3×CD137×CD276) that targeted CD3, CD137, and CD276, aiming to restrict the growth of TNBC tumors (4T1 model) and provide a novel therapeutic strategy. METHODS: The capacity for binding to target cells and anti-tumor effects of TsAb in vitro were evaluated. In vivo antitumor efficacy and biosafety were further assessed in the 4T1 subcutaneous tumor model. Anti-tumor immune responses induced by TsAb on tumor-infiltrating CD8 T cells were monitored. RESULTS: The TsAb effectively bound and facilitated interactions between 4T1 tumor cells and T cells, significantly boosting the anti-tumor effect. TsAb promoted the expansion of tumor and splenic T lymphocytes and facilitated the recruitment of splenic and blood T lymphocytes to tumor tissues. Compared with the PGLU-Fc-III-4C-IgG treatment group, the TsAb treatment group had varying degrees of increase in CD8 tissue-resident memory T cells (TRM), central memory T cells (TCM), and terminal effector memory T cells (TEM) in tumor tissues. The TsAb treatment group exhibited a significant increase of PD-1 CD8 T cells and TCF1Tim-3 CD8 terminally exhausted T cells in tumor tissues. The safety profile demonstrated no obvious systemic toxicity. DISCUSSION: Briefly, TsAb mediated CD8 T cell activation, proliferation, and terminal differentiation, accompanied by increasing cytokine production to eliminate the tumor. Meanwhile, no obvious systemic toxicity was observed. In general, the CD3×CD137×CD276 nanobioconjugate trispecific antibody provides a promising immunotherapeutic approach via regulating CD8 T cell immune response for the treatment of triple-negative breast cancer.
Nanomedicine-Based Therapeutic Approaches in Colorectal Cancer Using Patient-Derived Xenograft Models: Prospects and Challenges.
Wang X, Xiao J, Yang Y … +1 more , Li T
Int J Nanomedicine · 2026 · PMID 42311426 · Full text
Colorectal cancer is leading cause of morbidity and mortality worldwide. Advances in surgery, chemotherapy, and targeted therapies have improved treatment options, effective clinical management remains limited by tumor h...
Colorectal cancer is leading cause of morbidity and mortality worldwide. Advances in surgery, chemotherapy, and targeted therapies have improved treatment options, effective clinical management remains limited by tumor heterogeneity, resistance to therapy, and metastatic spread. In recent years, nanomedicine has gained attention as an effective strategy to address these challenges by improving drug delivery to tumor sites, enhancing bioavailability, and reducing systemic toxicity. Patient-derived xenograft models have become an important tool in preclinical cancer research because they preserve the histological and genetic characteristics of original human tumors and more closely reflect clinical disease behavior. This review summarizes recent advances in nanomedicine-based approaches for colorectal cancer treatment, with a particular focus on their evaluation using patient-derived xenograft models. A range of nanocarrier systems, including nanoparticles, liposomes, and dendrimers, have been explored for delivery of chemotherapeutic agents, biologics, and small-molecule inhibitors, demonstrating improved tumor targeting and therapeutic potential. Despite these encouraging developments, several challenges remain, including the complexity of tumor microenvironment, variability between patients, and concerns related to safety, scalability, and clinical translation. This review highlights current progress to enable the successful application of nanomedicine-based therapies for colorectal cancer in clinical practice.
Harnessing a cRGD-Targeted Schottky Junction MXene Nanocomposite for Potent Bladder Cancer Therapy: Dual-Modal PTT/PDT Effects with Immune Activation and Favorable Comparison to Doxorubicin.
Gu Z, Zhu H, Zhang Y … +3 more , Jiang J, Gu D, Chen J
Int J Nanomedicine · 2026 · PMID 42311425 · Full text
OBJECTIVE: This study developed a multifunctional MnFeO/TiVNbMoC-cRGD (MXenes) nanocomposite for targeted photothermal- photodynamic therapy against bladder cancer. METHODS: A multifunctional MXene-based nanocomposite wa...
OBJECTIVE: This study developed a multifunctional MnFeO/TiVNbMoC-cRGD (MXenes) nanocomposite for targeted photothermal- photodynamic therapy against bladder cancer. METHODS: A multifunctional MXene-based nanocomposite was constructed by integrating MnFeO nanoparticles onto TiVNbMoC MXene nanosheets to form a layer-on-layer Schottky junction, followed by conjugation of cRGD peptides for tumor targeting. Successful synthesis, colloidal stability, broad optical absorption, efficient photothermal conversion and ROS generation under 808 nm laser were confirmed. In vitro assays were conducted using 5637 bladder cancer cells, and a murine bladder tumor model was established to evaluate the anticancer efficacy. Biocompatibility assessments were also carried out. RESULTS: The composite was constructed by integrating MnFeO nanoparticles onto TiVNbMoC MXene nanosheets, which formed a layer - on - layer Schottky junction. Then, cRGD peptides were conjugated to the surface for tumor targeting. Comprehensive characterization confirmed successful synthesis, favorable colloidal stability, broad optical absorption, and efficient photothermal conversion and reactive oxygen species (ROS) generation under 808 nm laser irradiation. In vitro, the cRGD-targeted nanocomposite was efficiently internalized by 5637 bladder cancer cells and showed significantly higher anticancer efficacy than doxorubicin (DOX), including inhibition of proliferation, migration, colony formation, and induction of apoptosis and immunogenic cell death. In a murine bladder tumor model, the nanocomposite achieved the strongest tumor growth suppression and reduced final tumor volume more effectively than DOX. Biocompatibility assessments showed minimal hemolysis and no major organ damage at therapeutic doses. CONCLUSION: This MXene-based Schottky junction nanocomposite represents a promising targeted platform for dual-modal photothermal/photodynamic therapy combined with immune activation in bladder cancer, warranting further translational investigation.
Engineering Nanocarriers for Dopamine Stabilization and Targeted Brain Delivery: Mechanisms, Approaches and Translational Challenges.
Patra S, Nathani A
Int J Nanomedicine · 2026 · PMID 42311424 · Full text
Dopamine plays a central role in motor control, cognition, reward signaling, and neuroendocrine regulation, and its dysregulation is strongly associated with neurological disorders such as Parkinson's disease. However, c...
Dopamine plays a central role in motor control, cognition, reward signaling, and neuroendocrine regulation, and its dysregulation is strongly associated with neurological disorders such as Parkinson's disease. However, conventional dopaminergic therapies remain limited by poor blood-brain barrier (BBB) penetration, rapid systemic metabolism, short half-life, peripheral toxicity, and dopamine oxidation-induced neurotoxicity. Nanomedicine-based drug delivery systems have emerged as promising strategies to overcome these limitations by enhancing dopamine stability, improving BBB transport, enabling controlled release, and facilitating targeted delivery to dopaminergic brain regions. This review comprehensively summarizes current advances in dopamine-targeted nanotherapeutics, including polymeric nanoparticles, liposomes, solid lipid nanoparticles, dendrimers, inorganic nanoparticles, exosomes, and biomimetic vesicles. Particular emphasis is placed on the dual role of nanocarriers in both facilitating dopamine delivery and protecting dopamine from oxidative degradation and reactive oxygen species-associated toxicity. Among currently investigated platforms, polymeric nanoparticles, lipid-based nanocarriers, and exosome-inspired vesicles appear particularly promising due to their ability to improve dopamine stability, facilitate controlled release, enhance BBB penetration, and enable targeted brain delivery. The review additionally discusses receptor-mediated targeting strategies, intranasal delivery approaches, translational barriers, manufacturing scalability, long-term safety considerations, and regulatory challenges associated with clinical implementation. Finally, emerging future directions involving AI-assisted nanocarrier engineering, precision-targeted delivery systems, and stimuli-responsive nanomedicine are highlighted as promising approaches for the development of next-generation therapies for neurodegenerative disorders.
Gold Nanoparticle Radiosensitization for High-Dose-Rate Brachytherapy: Differential Efficacy of PEG- and RGD-Functionalized Gold Nanoparticles Across 2-Dimensional, 3-Dimensional, and in vivo Prostate Cancer Models.
Cecchi D, Jackson N, Karaman D … +4 more , Beckham W, Johnstone CD, Lloyd SAM, Chithrani D
Int J Nanomedicine · 2026 · PMID 42311423 · Full text
PURPOSE: Gold nanoparticles (GNPs) are promising radiosensitizing agents for radiation therapy; however, their implementation into high dose rate brachytherapy (HDR-BT) remains underexplored. Surface functionalization wi...
PURPOSE: Gold nanoparticles (GNPs) are promising radiosensitizing agents for radiation therapy; however, their implementation into high dose rate brachytherapy (HDR-BT) remains underexplored. Surface functionalization with polyethylene glycol (PEG) or integrin-binding domain RGD impacts their biodistribution and intracellular uptake, but whether active cellular targeting via RGD improves radiosensitization for HDR-BT has not been established in vivo. METHODS: Here, we systematically compare the radiosensitization efficacy of non-targeted PEGylated GNPs versus actively targeted PEG-RGD GNPs on PC3 prostate cancer cells in vitro and in vivo, using clinically plausible concentrations, dosing procedures, and purpose-built irradiation platforms. 2-dimensional (2-D) and 3-dimensional (3-D) cell cultures, and male NRG mice were irradiated via a 192-Ir source delivered from a clinical HDR-BT afterloader. In vitro samples were dosed at 10 μg [Au]/mL and mice were intratumourally injected with 50 μL at 2 mg [Au]/kg bodyweight. RESULTS: PEGylated GNPs did not elicit any radiosensitization either in 2-D, 3-D, or in vivo. RGD-functionalized GNPs elicited a 17% (0.001) reduction in survival fraction and 33% (=0.005) greater DNA DSBs in 2-D cell cultures, and 57% (<0.0001) reduction in 3-D spheroid growth compared to control samples 14 days post-irradiation. In a pre-clinical mouse xenograft model, tumour volume growth was also significantly reduced by 28% (0.005) 20 days post-irradiation compared to the irradiated control group, with no observable signs of acute toxicity from radiation delivery or administered GNPs. CONCLUSION: This research represents the first systematic in vitro and in vivo demonstration of GNP-induced radiosensitization using an HDR-BT source with clinically informed intratumoural delivery. Active cellular targeting with RGD functionalization was found to be a critical determinant of radiosensitization efficacy both in vitro and in vivo. Both GNP formulations demonstrated tolerability at the delivered dosing concentrations, and further research into the clinical deliverability of GNPs for HDR-BT is necessitated.
Nanomedicine in 2026: Illustrative Quantitative Analyses of EPR Heterogeneity, Clinical Trial Attrition, and Emerging Horizons for Active Nanotherapeutics.
Fayez SM
Int J Nanomedicine · 2026 · PMID 42311422 · Full text
2026 is a turning point for nanomedicine, marking the field's transition from decades of preclinical promise toward tangible clinical impact. This narrative review provides a forward-oriented synthesis of the most signif...
2026 is a turning point for nanomedicine, marking the field's transition from decades of preclinical promise toward tangible clinical impact. This narrative review provides a forward-oriented synthesis of the most significant clinical breakthroughs achieved during 2025-2026, critically examines persistent barriers to clinical translation, and projects future horizons for the coming decade. To support the discussion, the review includes illustrative quantitative analyses drawn from selected published data: a comparison of EPR effect heterogeneity across human and murine tumors (23 studies, 412 patients), a funnel of nanomedicine clinical trials extracted from ClinicalTrials.gov (847 trials, 2010-2020), a comparative overview of regulatory guidance from four major agencies, and a simplified life-cycle assessment of three nanomedicine classes. These analyses are intended to highlight trends, not to replace a formal systematic review. We identify four important clinical advances: first Phase II data for hafnium oxide nanoparticle radioenhancers in inoperable lung cancer; logic-gated STING-agonistic nanoparticles for metastasis-specific immunotherapy; ultrasmall silica nanoparticles that remodel suppressive tumor microenvironments independent of a drug cargo; and CNM-Au8 gold nanocrystals advancing toward regulatory submission for amyotrophic lateral sclerosis. Collectively, these developments illustrate a major change in thinking: nanoparticle formulations no longer serve merely as delivery vehicles but increasingly function as active therapeutic agents that engage biological pathways, respond to disease-associated stimuli, and generate therapeutic effects independently of any drug cargo. This shift from passive delivery to active nanotherapeutics fundamentally changes how the field should evaluate and develop nanomedicines. Nevertheless, the number of nanomedicines that have achieved global clinical approval remains very low, estimated at only 50-80 products by 2025, underscoring a persistent translational gap. We analyze principal obstacles to clinical success, including the limited predictive validity of the enhanced permeability and retention (EPR) effect in humans, batch-to-batch manufacturing variability, safety concerns arising from bio-corona formation and organ accumulation, and the absence of harmonized regulatory frameworks. Looking forward, we identify emerging horizons: AI-driven digital twins for predictive manufacturing, carrier-free self-assembled nanomedicines from natural small molecules, nanotheranostic platforms that integrate therapy with real-time imaging, and sustainable nanomedicine designs incorporating environmental impact assessments. By bridging clinical reality with future potential, this review aims to inform researchers, clinicians, and regulatory stakeholders navigating the rapidly evolving landscape of nanomedicine.
Nanotechnology-Enhanced Vaccines for Respiratory Infections: Opportunities and Challenges.
Wang K, Jiang Y, Zhou Y
Int J Nanomedicine · 2026 · PMID 42311421 · Full text
The continued global burden of the respiratory infections, despite availability of effective vaccines against major respiratory pathogens, represents the need to improve vaccination strategies. Although the conventional...
The continued global burden of the respiratory infections, despite availability of effective vaccines against major respiratory pathogens, represents the need to improve vaccination strategies. Although the conventional vaccines have shown effectiveness in many of the infectious diseases, they have serious limitations in developing the mucosal immunity and often fail to provide long-term protection against the rapidly mutating respiratory pathogens. In this area, nanotechnology offers novel solutions to enhance the potential of the respiratory vaccines. This review highlights recent advancements in the diverse nanotechnology platforms for respiratory vaccines, along with their transformative potentials, opportunities as well as challenges by covering the recent trends in the nanotechnology-based respiratory vaccines. Various nanotechnology platforms for respiratory vaccines include lipid nanoparticles (LNPs), polymeric nanoparticles, inorganic nanoparticles, biomimetic and self-assembling nanoplatforms. These platforms potentially address the key limitations of the traditional respiratory vaccines by improving the stability and targeted delivery of antigens, mucosal and cellular immune responses and flexible formulations against the evolving pathogens. However, challenges related to safety, scalability and real world applicability remain. The increasing research endeavors are gradually addressing the longstanding challenges and limitations of the nanotechnological measures in the respiratory vaccination and advancing this field with new opportunities for preventing the respiratory infections.
Intranasal Delivery of Curcumin-Loaded Pure Drug Self-Assembled Lipid-Based Nanoparticles for Targeted Therapy of Depression.
Chen T, Liu X, Li D … +3 more , Cheng Z, Zheng X, Yu Z
Int J Nanomedicine · 2026 · PMID 42311420 · Full text
PURPOSE: Current antidepressants are limited by insufficient efficacy of conventional monoaminergic drugs and poor brain penetration across the blood-brain barrier. This study designed pure curcumin loaded lipid nanopart...
PURPOSE: Current antidepressants are limited by insufficient efficacy of conventional monoaminergic drugs and poor brain penetration across the blood-brain barrier. This study designed pure curcumin loaded lipid nanoparticle (CNP) with optimized brain-targeting delivery for depression therapy. METHODS: Cur molecules first self-assembled into carrier-free drug nanoparticles. Subsequently, CNP were then prepared via thin-film dispersion and fully characterized in terms of particle size, PDI, DSC, XRD, TEM. The antidepressant effect of CNP was systematically investigated via in vitro and in vivo assays, including cellular uptake, LPS-induced stress model in BV2 cells, and in vivo CUMS depression model. RESULTS: CNP displayed uniform spherical morphology with an average size of 115.8 ± 18.3 nm, PDI of 0.216 ± 0.015 and zeta potential of -27.1 mV, along with high encapsulation efficiency (86.11 ± 4.28%), drug loading (6.62 ± 0.45%) and sustained release behavior. The cellular uptake efficiency of the CNP group reached 41.47 ± 1.45%, which was more than double that of the Cur group (17.21 ± 0.54%). In vitro studies showed that CNP not only rescued the viability of cells damaged by corticosterone and hydrogen peroxide but also exerted significantly enhanced anti-inflammatory and antioxidant effects in lipopolysaccharide induced cellular stress models. In vivo studies indicated that CNP alleviated depressive-like behaviors more effectively. CONCLUSION: CNP exhibits significantly enhanced antidepressant efficacy, thus providing a promising approach for developing brain-targeted therapeutics for MDD.
Neutrophil-Membrane Biomimetic Hollow Mesoporous Silica Nanoparticles for Targeted Delivery of Imperatorin to Alleviate Cerebral Ischemia-Reperfusion Injury via Nrf2/ARE/Keap1 Pathway.
Chen F, Jiang H, Song X … +8 more , Wang J, Ma X, Zhou Q, Mamun AA, Li L, Zhou Y, Xu H, Wang S
Int J Nanomedicine · 2026 · PMID 42305693 · Full text
INTRODUCTION: Cerebral ischemic stroke has high mortality and disability rates with limited targeted therapeutic strategies. Biomimetic nanocarriers can optimize drug delivery efficiency and exert neuroprotection effects...
INTRODUCTION: Cerebral ischemic stroke has high mortality and disability rates with limited targeted therapeutic strategies. Biomimetic nanocarriers can optimize drug delivery efficiency and exert neuroprotection effects, providing a promising strategy for ischemia-reperfusion injury treatment. METHODS: Hollow mesoporous silica nanoparticles (HMSNs) were synthesized via an improved Stoer method and loaded with imperatorin (IMP). Subsequently, neutrophil cell membranes (NCM) extracted from DMSO-induced HL-60 cells were coated onto the nanoparticles to construct NCM/IMP@HMSNs. Nanomaterial characterization was carried out. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) models in SH-SY5Y cells and in vivo rat middle cerebral artery occlusion/reperfusion (MCAO/R) models were established to explore the underlying neuroprotective mechanisms. RESULTS: The synthesized NCM/IMP@HMSNs nanoparticles possessed uniform particle size (~143 nm) and favorable stability, with an encapsulation efficiency of 31.84%. In vitro results revealed that IMP significantly increased the viability of OGD/R-injured SH-SY5Y cells compared with the model group. In vivo experiments showed that NCM/IMP@HMSNs efficiently accumulated in ischemic brain tissue, notably decreased mNSS scores, and reduced cerebral infarct volume by approximately 33.31% compared with the MCAO/R group. This nanosystem activated the Nrf2/ARE/Keap1 pathway, thereby upregulating HO-1 expression to strengthen antioxidant capacity, alleviate the accumulation of cerebral oxidative stress products, and regulate the activities of SOD, GSH, CAT and LDH. CONCLUSION: The biomimetic NCM/IMP@HMSNs nanoplatform enhances the neuroprotective efficacy against ischemia-reperfusion injury via activating the Nrf2/ARE/Keap1 pathway, offering a promising targeted therapeutic approach for ischemic stroke therapy.
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