International Journal of Nanomedicine最新文献

Diabetic foot ulcers (DFUs) are one of the most serious and intractable complications of diabetes, caused by oxidative stress due to hyperglycemia, chronic inflammation, and repeated infections. Conventional treatments such as insulin therapy do not improve the pathological wound microenvironment, resulting in slow healing and a high rate of recurrence. Nanozymes, with superior catalytic stability, tuneable enzyme-like activities, and multifunctional synergy, have emerged as a promising therapeutic strategy. Nanozymes that imitate natural enzymes such as glucose oxidase, peroxidase, catalase, and superoxide dismutase can actively remodel the DFUs microenvironment via glucose depletion, dynamic regulation of reactive oxygen species, disruption of biofilm, suppression of inflammation, and oxygen generation. These integrated functions can help wounds heal faster, and they can promote angiogenesis and tissue regeneration. This review discusses recent advances in catalytic mechanisms and therapeutic applications of nanozymes for DFUs management, with special attention paid to the microenvironment-responsive systems, hydrogel-based composites, and synergistic photothermal or drug delivery platforms. Lastly, the current issues of biosafety, catalytic efficiency, and target accuracy are mentioned, followed by future directions for clinical application.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease commonly managed with topical corticosteroids or calcineurin inhibitors, which may raise concerns with long-term use. Safe, non-steroidal topical therapies capable of restoring skin barrier function while modulating local immune responses remain limited.

Methods: A sacchachitin nanofiber (SCNF)-based hydrogel incorporating melatonin (MSC) was developed and evaluated for physicochemical properties, stability, and therapeutic efficacy using a 2,4-dinitrochlorobenzene (DNCB)-induced NC/Nga mouse model of AD. Clinical scores, histological features, and immunological biomarkers were assessed.

Results: Among the tested formulations, the melatonin-loaded hydrogel (MSC) demonstrated the most pronounced therapeutic efficacy compared with other formulations, significantly reducing AD severity, epidermal hyperplasia, mast cell infiltration, and Th2-associated markers including IgE, IgG1, and IL-4. Melatonin remained chemically stable for at least 31 days and did not compromise hydrogel mechanical or adhesive properties. In this system, sacchachitin nanofibers primarily function as a structural scaffold, whereas melatonin provides the principal biological and immunomodulatory activity.

Conclusion: The melatonin-loaded SCNF hydrogel represents a promising non-steroidal and biocompatible topical platform for AD. In this system, SCNF primarily serves as a structural scaffold, whereas melatonin provides immunomodulatory and anti-inflammatory activity. These findings support further translational investigation.

Tumor-derived circulating cell-free DNA (ctDNA) has emerged as a pivotal biomarker for non-invasive cancer diagnosis, treatment monitoring, and prognostic evaluation. However, its inherently low abundance, high fragmentation, and rapid degradation impose stringent requirements on assay sensitivity, specificity, and analytical robustness. Rapid advances in nanotechnology have significantly accelerated progress in ctDNA detection. This review summarizes recent nanotechnology-assisted strategies for ctDNA analysis, including surface-engineered nanomaterials for selective enrichment, nano-enabled signal amplification modalities, and integrated platforms such as CRISPR-based detection, microfluidics and nanopore technologies. We further highlight nanostructure-based approaches for decoding methylation, fragmentation profiles, and multi-omics signatures, focusing on their potential to enhance early cancer detection and real-time therapeutic assessment. Moreover, increasing incorporation of artificial intelligence (AI) which spans nanostructure characterization, aptamer and probe design, multi-omics data integration, and algorithm development is reshaping the landscape of nano-assisted liquid biopsy. Finally, current challenges and future perspectives concerning the clinical translation of nanotechnology-assisted ctDNA detection are presented, emphasizing standardization, biocompatibility, automation, and regulatory readiness. Overall, this review provides a comprehensive outlook on how converging nanotechnology and AI innovations are advancing ctDNA-based precision oncology.

Osteosarcoma (OS) is the most common primary malignant bone tumor, with two incidence peaks: one in adolescence and the other in older individuals. Despite significant research, patient prognosis has not substantially improved in recent decades because of a limited understanding of its pathogenesis and a lack of innovation in treatment approaches. The tumor microenvironment (TME) is a rapidly evolving area of cancer therapy, offering critical insights into the dynamics of osteosarcoma development at the cellular and molecular levels. This study also provides valuable guidance for the development of novel therapeutic strategies. To date, a broad array of nanomedicines have been engineered to target specific ligands within the OS TME. Compared with conventional chemotherapeutic agents, these nanomedicines can substantially enhance drug delivery efficiency while minimizing off-target side effects. In this review, we focus on nanomedicines that target the TME of osteosarcoma. We first explore the core components of the OS TME, which include osteoblasts, mesenchymal stem cells, the vascular microenvironment, and immune cells. Subsequently, we delve into the latest advances and biomedical applications of nanodrug delivery systems engineered specifically for targeting the TME of osteosarcoma. The findings of this review aim to contribute to improved treatment options and outcomes for osteosarcoma patients.

Background: Androgenetic alopecia (AGA) is characterized by hair follicle miniaturization and growth factor deficiency. However, conventional therapies such as minoxidil and finasteride fail to restore the pathological follicular microenvironment, highlighting the urgent need for novel therapeutic strategies. Epidermal growth factor (EGF) and fibroblast growth factor (FGF) are key regulators of hair follicle regeneration, yet their expression is downregulated in the follicular microenvironment of AGA patients.

Methods: This study validated the expression profile of growth factors in hair follicles of AGA patients through clinical sample analysis. Subsequently, dual‑factor engineered exosomes (EXO‑EGF/FGF) loaded with EGF and FGF were constructed using LAMP2B fusion engineering technology with 293T cells as donor cells. EXO‑EGF/FGF was characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The regulatory effects of EXO‑EGF/FGF on human dermal papilla cells (HDPCs) were evaluated in vitro. An androgen‑induced AGA mouse model was established to assess the therapeutic efficacy and safety of EXO‑EGF/FGF in vivo.

Results: Clinical sample analysis confirmed that the expression of EGF and FGF was significantly downregulated in dermal papilla cells of AGA patients, leading to reduced expression of NOTCH signaling pathway proteins associated with hair follicle regeneration. TEM and NTA results demonstrated that EXO‑EGF/FGF exhibited exosomal morphology, with significantly higher expression levels of EGF and FGF than natural exosomes. In vitro experiments revealed that EXO‑EGF/FGF promoted the proliferation and migration of HDPCs by reactivating the cell cycle and enhancing migration‑related programs. In the AGA mouse model, EXO‑EGF/FGF effectively restored hair coverage density and follicular structural integrity without inducing immunogenic reactions or systemic toxicity, and significantly increased the number of anagen‑phase hair follicles in post‑treatment tissues.

Conclusion: This study demonstrated that LAMP2B‑engineered EXO‑EGF/FGF acted on follicular cells to repair the pathological microenvironment in AGA. This strategy overcame the inherent limitations of conventional therapies and natural exosomes, offering a novel, safe, and clinically translatable therapeutic approach for AGA treatment.

Background: Melanoma is a highly metastatic skin cancer with occult early symptoms, making sensitive diagnostic tools essential for early intervention. Tyrosinase (TYR), a key enzyme in melanogenesis, is aberrantly secreted into the bloodstream by melanoma cells and thus serves as a promising biomarker for melanoma. However, the ultralow concentration of TYR in serum (0.066-0.636 U/L) poses a significant challenge to conventional detection methods, highlighting the need for more sensitive detection strategies.

Methods: An electrochemical biosensor was engineered using a screen-printed electrode (SPE) as the base. The SPE was modified with a nanocomposite consisting of tyramine-functionalized carboxylated multi-walled carbon nanotubes (MWCNTs-tyr), gold nanoparticles (Au NPs), and poly(3,4-ethylenedioxythiophene) (PEDOT). To validate the sensor's performance, differential pulse voltammetry (DPV) was employed, with tests conducted in phosphate-buffered saline (PBS, pH 7.0) and murine serum samples.

Results: The MWCNTs-tyr/Au NPs/PEDOT nanocomposite synergistically enhanced the sensor's conductivity, catalytic activity, and TYR-specific binding capacity. The sensor exhibited a wide linear detection range for TYR (0.05~0.9 U/L, R² = 0.9914), and a low detection limit of 0.0091 U/L. Additionally, it showed excellent reproducibility (5 consistent measurements at a TYR concentration of 0.1 U/L) and high specificity against common serum interferents. In tumor-bearing mice, TYR serum levels were found to correlate with tumor progression: TYR concentration was 0.084 ± 0.009 U/L when tumor volume was 68 ± 5.25 mm³, and increased to 0.653 ± 0.028 U/L when tumor volume reached 1280 ± 89.22 mm³.

Conclusion: This study presents a proof-of-concept for a MWCNTs-tyr/Au/PEDOT/SPE biosensor. The platform enables rapid and sensitive detection of TYR in small-volume samples and effectively monitors tumor burden in a murine model, demonstrating its potential as a research tool for melanoma biomarker investigation.

Background: Postoperative recurrence of glioma remains a major clinical challenge due to the blood-brain barrier and an immunosuppressive tumor microenvironment, necessitating innovative local treatment strategies.

Methods: We developed a biomimetic nanoplatform (CaDM) by coating doxorubicin (DOX)-loaded calcium carbonate nanoparticles with a glioma cell membrane. This construct was then integrated with the clinical hemostatic agent Surgiflo to create an in-situ forming depot for localized application into the tumor resection cavity.

Results: The CaDM nanoparticles exhibited excellent acid-responsive degradation, enabling simultaneous release of DOX and Ca²⁺ in the tumor microenvironment. This co-delivery initiated a potent synergistic antitumor effect: DOX induced direct cytotoxicity and immunogenic cell death (ICD), while Ca²⁺ influx triggered calcium overload, mitochondrial damage, and tumor vascular thrombosis. Furthermore, CaCO₃ degradation neutralized the acidic microenvironment, downregulating cathepsin B to reverse immunosuppression. In the postoperative glioma model, CaDM@Surgiflo significantly suppressed tumor recurrence and extended the median survival of mice from 14 days to 40 days. Mechanistic studies revealed that this localized therapy amplifies the ICD cascade through the combined action of DOX and Ca²⁺ overload, which in turn robustly activates dendritic cells and augments the infiltration of cytotoxic T lymphocytes.

Conclusion: This work presents a readily translatable and multifaceted nanomedicine approach that effectively prevents glioma recurrence through synergistic calcium overload and immunomodulation, offering a promising novel strategy for local tumor treatment.

Background: Paclitaxel is a cornerstone of breast cancer treatment, but its efficacy is often limited by low response rates and drug resistance. To address this, we developed MEVs@CuET, a novel therapeutic approach combining cuproptosis-inducing copper(II) complex (CuET) with macrophage-derived extracellular vesicles (MEVs), aiming to enhance paclitaxel's antitumor effects.

Methods: The tumor-targeting capability of MEVs@CuET was evaluated through cellular uptake and in vivo distribution studies. In vitro synergy was assessed using the ZIP model, while transcriptome sequencing analyzed gene expression changes. In vivo antitumor activity and immune modulation were examined in breast cancer models, with tumor growth inhibition, apoptosis, and Th17 lymphocyte levels measured.

Results: MEVs@CuET demonstrated efficient tumor targeting and synergistic antiproliferative effects with paclitaxel in vitro (synergy score: 29.37). Transcriptomic analysis revealed significant alterations in immune-related pathways, particularly upregulation of the IL-17 signaling pathway. In vivo, the combination therapy markedly inhibited tumor growth, increased apoptosis, and elevated Th17 cell levels, aligning with the transcriptomic findings.

Conclusion: MEVs@CuET significantly enhances paclitaxel's efficacy by inducing cuproptosis and modulating antitumor immunity, offering a promising strategy to overcome resistance in breast cancer treatment.

This narrative review summarizes recent advances in gelatin methacryloyl (GelMA)-based nanocomposites for bone defect regeneration, addressing the persistent clinical need for effective and customizable bone repair strategies. As an extracellular matrix (ECM)-mimicking hydrogel, GelMA offers favourable biocompatibility, tunable mechanics, and photo-crosslinkability, enabling integration with light-based 3D printing platforms to fabricate patient-specific scaffolds and, more recently, skeletal organoid-inspired constructs. Nevertheless, key barriers to translational advancement remain, including limited load-bearing capacity without reinforcement, insufficient vascularization, lack of intrinsic antibacterial activity, and a shortage of large-animal validation and well-designed clinical trials. We synthesize how formulation and processing parameters translate into scaffold properties and biological outcomes, and we discuss representative optimization strategies-such as composite reinforcement with hydroxyapatite/bioglass, bioactive molecule delivery, and immunomodulatory design-to address these limitations. We further highlight application-oriented evidence across major bone-loss-related conditions and summarize practical translational bottlenecks, including batch-to-batch reproducibility, scalable, GMP-compliant pathways that may be required, sterilization compatibility, and the need to synchronize degradation kinetics with new bone formation. By integrating material design, mechanistic considerations, and translational constraints, this review provides a framework to guide the rational development of GelMA-based systems toward clinically relevant bone regeneration.

Background: Background: Alcohol-related liver disease (ALD) is the leading cause of liver disease-related deaths globally, necessitating new treatments. This study investigates the role of long intergenic noncoding RNA (lincRNA)-p21 in ALD and explores therapeutic strategies for liver injury.

Methods: We identified lncRNAs linked to ethanol-induced liver injury using the Gene Expression Omnibus (GEO) database. Experiments were conducted to assess the function of lincRNA-p21 in ALD both in vivo and in vitro. Autophagy was analyzed through electron microscopy, autophagic flow, and protein expression. Bioinformatics explored underlying mechanisms, focusing on m6A modification of lincRNA-p21 by ALKBH5 using RNA Immunoprecipitation (RIP) and meRIP-PCR. Ferroptosis was induced with erastin, and its levels were measured by cell ROS and viability. A nanoplatform-based system was developed to co-deliver a plasmid encoding lincRNA-p21 and a ferroptosis inhibitor. We developed a nanoplatform-based co-delivery system to deliver a plasmid encoding lincRNA-p21 and the ferroptosis inhibitor ferrostatin-1 (ferr-1/lincRNA-p21@NP) to the liver.

Results: LincRNA-p21 protected liver cells against ethanol-induced injury by promoting autophagy. ALKBH5 mediated the m⁶A demethylation and lincRNA-p21 upregulation. However, we revealed a dual-edged sword function for lincRNA-p21 in ethanol-induced liver injury in mice. LincRNA-p21 reduced acute ethanol-induced cell injury by enhancing autophagy but exacerbated chronic ethanol-induced liver cell injury by increasing ferroptosis. In vivo and in vitro analyses showed favorable therapeutic effects of ferr-1/lincRNA-p21@NPs on ALD.

Conclusion: These results show that lincRNA-p21 affects autophagy and ferroptosis, and the ferr-1/lincRNA-p21@NP nanosystem can provide protection against ALD.