International Journal of Nanomedicine最新文献

Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and teenagers, characterized by aggressiveness and early metastasis especially to the lungs. OS management is complex and combined-modality therapy involving surgery, chemotherapy and immunotherapy is common. The standard care treatment utilizing doxorubicin, cisplatin, and high-dose methotrexate is a combination ("MAP") not changed in more than 40 years that often confronts incomplete tumor removal, recurrence, drug resistance, and severe side effects. Recent advancements in nano- and precision medicine have introduced tumor-targeted drug delivery strategies through multifunctional nanocarriers which aim to enhance therapeutic efficacy by preventing rapid clearance, prolonging circulation time and improving accumulation at tumor sites while minimizing adverse effects. Although many of these smart Nanotherapeutics are still at the preclinical stage, their unique properties make their promotion in OS clinical applications a challenge. Starting from an overview of the current approved OS therapies, this review reports a systematic analysis of in vivo studies published in the last decade that employ multifunctional nanosystems, drug delivery strategies and cutting-edge technologies in chemo-, immuno- and gene therapy for OS management providing an overview of the potential and challenges of these innovative treatment strategies. Our comprehensive literature analysis points out their certain antitumoral effects in OS preclinical models; however, overcoming translational bottlenecks remains a critical challenge, as promising preclinical findings often fail to translate into effective clinical therapies. Moreover, extended long-term observation in clinical studies is still required together with an in-depth understanding of the unique genetics and biology of OS, given the complex heterogeneity of the tumor microenvironment. By analyzing the limitations of conventional therapies, the latest advancements in nanotechnology alongside key bottlenecks in clinical translation of nanotherapeutics for OS, this review provides valuable insight into future directions, particularly for combination regimens, fostering progress in OS clinical research and supporting the development of innovative and personalized therapies.

Objective: This research explored the effectiveness of RGD peptide-functionalized gold nanoparticles (AuNPs) loaded with the histone deacetylase inhibitor SAHA (suberoylanilide hydroxamic acid) to enhance the radiosensitivity of non-small cell lung cancer (NSCLC) by suppressing hypoxia signaling, thereby mitigating oxidative stress and inflammatory responses.

Methods: RGD-AuNPs-SAHA was synthesized via citrate reduction, thiol-gold bonding for RGD modification, and SAHA loading. Structural and chemical characteristics were assessed via dynamic light scattering (DLS), transmission electron microscopy (TEM), UV-Vis spectroscopy, high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). Elemental distribution was mapped using TEM-EELS. Drug release behavior was evaluated under neutral and acidic conditions (pH 7.4 and 5.5). SAHA release kinetics were assessed at pH 7.4 and 5.5. Cellular uptake and biodistribution were evaluated in A549 cells and xenograft mice using fluorescence labeling and flow cytometry. Therapeutic efficacy was examined via tumor volume measurement, serum cytokine profiling (TNF-α, IL-6, IL-10), oxidative stress markers (SOD, CAT, MDA), and molecular analyses (IHC, IF, Western blot, RT-PCR). DNA damage and apoptosis were quantified using TUNEL and γ-H2AX staining.

Results: RGD-AuNPs-SAHA exhibited uniform size (~20 nm), high SAHA encapsulation (85.2%), and pH-responsive release (60% at pH 5.5 vs 35% at pH 7.4). XPS and EELS mapping further verified the formation of Au-S bonds between thiol-modified RGD and the AuNP surface. Quantitative analysis of surface-bound RGD peptides was performed using UV-Vis spectroscopy combined with the Levenberg-Marquardt algorithm. In vivo, RGD-AuNPs-SAHA reduced tumor volume by 60% and modulated inflammatory cytokines (↓TNF-α/IL-6, ↑IL-10). Oxidative stress markers improved significantly (SOD: 110 U/mL; CAT: 85 U/mL; MDA: ↓2 nmol/mL). Hypoxia signaling proteins HIF-1α and VEGF decreased by 50% and 40%, respectively, confirmed by Western blot and RT-PCR. Apoptosis and DNA damage markers increased by 70% (TUNEL) and 65% (γ-H2AX), demonstrating enhanced radiosensitization.

Conclusion: RGD-AuNPs-SAHA effectively remodeled the hypoxic tumor microenvironment, attenuated oxidative stress, and suppressed pro-tumorigenic signaling, leading to significant apoptosis and DNA damage. These findings highlight its potential as a radiosensitizer for NSCLC, offering a promising strategy to improve radiation therapy outcomes.

Purpose: To investigate the therapeutic potential of sulfur vacancy-molybdenum disulfide/carbon composite nanosheets (MoS_2-x/C NS) in Aspergillus fumigatus (A. fumigatus) keratitis in mice.

Methods: The in vitro antifungal efficacy of MoS_2-x/C NS against A. fumigatus was evaluated by propidium iodide (PI) staining, minimum inhibitory concentration (MIC) determination, and biofilm formation assays. Toxicity assessments of the MoS_2-x/C NS were conducted using a Lactate dehydrogenase (LDH) assay kit for in vitro cytotoxicity and the Draize eye test for in vivo ocular irritation. The severity of fungal keratitis in mice was assessed using clinical scoring, plate counting, and hematoxylin and eosin (H&E) staining. The anti-inflammatory efficacy of MoS_2-x/C NS was determined by quantifying inflammatory factor levels using reverse transcription polymerase chain reaction (RT-PCR).

Results: In vitro, MoS_{2 -x}/C NS significantly inhibited A. fumigatus growth, demonstrated favorable biocompatibility, and reduced the expression of IL-6 and TNF-α in human corneal epithelial cells (HCECs) stimulated by inactivated A. fumigatus hyphae. In vivo, MoS_{2 -x}/C NS treatment significantly reduced fungal load, attenuated pathological corneal damage, and suppressed IL-6 and TNF-α levels, effectively alleviating A. fumigatus keratitis in mice.

Conclusion: This study demonstrates that MoS_2-x/C NS possesses significant therapeutic potential for fungal keratitis mediated through dual antifungal and anti-inflammatory mechanisms, thereby improving the prognosis of A. fumigatus keratitis.

Immunotherapy is emerging as a powerful strategy against cancer; however, its efficacy is often blunted by the immunosuppressive tumor microenvironment (TME). Immunogenic cell death (ICD) can tilt this balance by releasing tumor-associated antigens and damage-associated molecular patterns that enhance TME immunogenicity, promote antigen-presenting cell maturation, and activate effector T cells. Ionizing radiation and doxorubicin (Dox) are two types of the common ICD inducers. However, they have severe off-target toxicities and limited therapeutic indices. To overcome these challenges, safe and natural products are now drawing widespread attention. Hypericin, a naturally occurring photosensitizer derived from the traditional Chinese herb Hypericum perforatum (St. John's wort), has been used medicinally for centuries, and is now recognized for its potent antimicrobial, antiviral, anti-inflammatory, and anticancer properties. Recent studies have revealed that hypericin can modulate tumor immunity, and when employed in photodynamic therapy (PDT) or sonodynamic therapy (SDT) it generates reactive oxygen species that trigger endoplasmic reticulum stress-mediated ICD. Nanocarrier-mediated delivery further amplified these effects by enhancing hypericin solubility, tumor accumulation, and ROS yield upon light irradiation. This minireview synthesizes the current knowledge on the immunomodulatory actions of hypericin within the tumor microenvironment, evaluates its performance as a PDT/SDT-based ICD inducer, and highlights that nanosized formulations of hypericin may accelerate the development of novel ICD inducers and immunomodulators.

[This retracts the article DOI: 10.2147/IJN.S132984.].

Introduction: Carbon dot nanoparticles (CNDs) are widely regarded as biocompatible agents for cellular imaging due to their strong fluorescence and ease of synthesis. However, their biological effects remain insufficiently characterized.

Methods: We synthesized carbon nanodots (E-CNDs) using a microwave-assisted method with citric acid and ethylenediamine. Their intracellular distribution and potential impact on triple-negative breast cancer (TNBC) cells were investigated.

Results: After 16 hours of incubation with E-CNDs (up to 0.8 mg/mL), imaging revealed strong perinuclear localization, moderate mitochondrial presence, and no detectable nuclear signal. These observations supported their use in intracellular imaging and motivated further analysis of their biological effects. While CCK-8 assays showed no significant cytotoxicity across concentrations, molecular analysis revealed dose-dependent downregulation of glucose-6-phosphate dehydrogenase (G6PDH) and upregulation of procaspase 3, aligning with increased apoptotic activity detected by Annexin V/PI staining.

Conclusion: These results show that although E-CNDs appear non-toxic by standard viability assays and function effectively as imaging agents, they also trigger measurable molecular and apoptotic responses. This underscores that cell viability alone is insufficient to assume biocompatibility. More detailed molecular and functional assessments are needed to establish reliable safety profiles, which are critical for the safe design and evaluation of nanomaterials in biomedical applications.

Background: Psoriasis is a long-term inflammatory skin disorder that significantly impacts the physical and psychological well-being of those affected. Curcumin (Cur) is a natural compound that holds promise for the topical management of psoriasis. However, the barrier property of the stratum corneum (SC) and the insufficient retention ability of the drug in the skin have severely restricted the clinical efficacy of Cur. To overcome these limitations, we introduced mussel adhesive protein (MAP) for its superior bioadhesive properties, and developed Cur-loaded MAP modified Pluronic F127 micelles (MAP-F127/Cur) to improve the skin permeation and retention of Cur and enhance the therapeutic effect on psoriasis.

Methods: In this study, MAP-F127 was synthesized via chemical synthesis. MAP-F127/Cur was prepared using the thin-film hydration method, and the physicochemical properties of the formulation were characterized. In addition, porcine skin was employed as an in vitro model to evaluate the skin permeation of the formulation and to elucidate the interaction mechanism between the formulation and the skin. Furthermore, the therapeutic efficacy of the formulation against psoriasis was assessed using an imiquimod-induced psoriasis mouse model.

Results: The prepared MAP-F127/Cur had a regular spherical shape and good dispersion, and could efficiently load Cur in the amorphous form. The skin retention of MAP-F127/Cur was notably elevated in comparison to both the Cur-loaded Pluronic F127 micelles (F127/Cur) and Cur solution (p<0.01). Studies on the skin permeation mechanism showed that MAP-F127/Cur could break through the restriction of the skin barrier by regulating lipid arrangement and keratin conformation in the SC, forming a long-acting drug reservoir in the epidermal layer. Furthermore, in the imiquimod-induced psoriasis mouse model, MAP-F127/Cur demonstrated a significantly enhanced therapeutic effect.

Conclusion: This study not only provides a new delivery strategy for Cur in the treatment of psoriasis, but also offers an important reference for designing transdermal delivery systems for other dermatological drugs.

Regulatory T cells (Treg cells) play a crucial role in maintaining immune tolerance and regulating immune responses, especially in cancer, where their immunosuppressive function is highly significant. Treg cells accumulate in the tumor microenvironment (TME), interact with tumor cells and other immune cells, and suppress anti-tumor immunity through various mechanisms, including secretion of immunosuppressive cytokines, direct contact with target cells, and depletion of key nutrients and signaling molecules. Regulating Treg cells has become a novel approach for enhancing cancer immunotherapy. Extracellular vesicles (EVs) are small vesicles with a lipid bilayer membrane secreted by all cells and play an important role in tumor biology as communication mediators by transmitting proteins, RNA, and other bioactive molecules in TME. In the past years, an increasing amount of research has uncovered the effects of EVs on Treg in TME, greatly enriching our understanding of Treg in tumor progression. Additionally, due to the potential of EVs as "natural nanoparticles" for drug and gene delivery, targeting Treg via an EV-delivery system has become a hotspot. Therefore, we comprehensively summarized the updates on the effects of EVs on Treg in TME and EV-related therapy for tumor treatment.

Mitochondrial dysfunction represents a pivotal pathological mechanism underlying diverse diseases, particularly those affecting the central nervous system (CNS). Consequently, therapeutic strategies capable of effectively restoring mitochondrial function hold significant promise for treating CNS disorders. Nanotechnology has emerged as a powerful platform in this endeavor, leveraging the modifiability, controllability, and targeting capabilities of nanosystems to intervene at the mitochondrial level. This review delineates the critical role of mitochondrial integrity in CNS pathophysiology and summarizes key mitochondria-targeting strategies, including small-molecule ligands, mitochondrial-penetrating peptides, mitochondrial membrane-derived vesicles, and biomimetic membrane coatings. We also discuss the efficacy of mitochondria-targeted nanosystems in rescuing mitochondrial dysfunction across major CNS conditions, exemplified by neurodegenerative diseases, brain tumors, ischemic stroke, and traumatic brain injury. Ultimately, this review also points out current translational challenges and future research directions pivotal for advancing mitochondrial nanomedicine. Collectively, this work synthesizes progress in mitochondrial nanotherapeutics, highlighting their transformative potential while outlining critical barriers and opportunities for clinical translation in CNS disorders.

Carbon nanomaterials have garnered significant interest from researchers acROSs various disciplines, primarily due to their high specific surface area, versatile surface chemical modifications, and exceptional optical properties. Notable carbon nanomaterials include graphene, carbon nanotubes, and carbon quantum dots, each exhibiting distinct potential applications within the biomedical domain. Extensive research over the years has positioned these diverse carbon nanoparticles as promising candidates for drug delivery, cancer diagnosis and therapy, tissue engineering, and biosensing, among other applications. Nonetheless, the issue of toxicity associated with carbon nanomaterials presents a pressing challenge that necessitates resolution. Empirical studies indicate that the size, aggregation state, and surface functionalization of carbon nanotubes can influence the biotoxicity and immunotoxicity of carbon nanoparticles within biological systems, thereby impacting their clinical translation and application. To advance the application and clinical translation of carbon nanomaterials within the biomedical field, this review will focus on carbon quantum dots, carbon nanotubes, graphene nanoparticles, and other carbon-based nanomaterials. It will provide a comprehensive summary of their application progress in the biomedical sector, as well as an analysis of their biotoxicity and immunotoxic responses. This synthesis aims to facilitate the clinical translation and application of carbon nanomaterials.