International Journal of Nanomedicine最新文献

[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.

Introduction: The detection of acetylcholinesterase (AChE) activity and the screening of its inhibitors are of significant importance for the diagnosis and drug therapy of nervous system diseases, particularly neurodegenerative disorders. This study aimed to develop a novel, integrated point-of-care testing (POCT) platform to address this need.

Methods: We designed and integrated a colorimetric biosensor (Colorisensor) that combines a microneedle array with a metal-phenol nanozyme. The core sensing element is Iron (III)-polydopamine (Fe-PD) nanorods, which exhibit high peroxidase-like activity. The detection mechanism is based on the AChE-catalyzed hydrolysis of acetylthiocholine (ATCh) to produce thiocholine (TCh), which inhibits the nanozyme's activity. This inhibition prevents the catalytic oxidation of the chromogenic substrate TMB, leading to a measurable color change. A smartphone was utilized to quantify this change via red, green, and blue (RGB) values, creating a rapid and user-friendly platform for detections of AChE activity and its drug inhibitor. The nanorods and microneedle arrays were characterized using scanning electron microscopy, high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy, ultraviolet-visible spectrophotometer, water absorption expansion rate, as well as mechanical property tests.

Results and discussion: The proposed Colorisensor demonstrated excellent analytical performance, including high selectivity and sensitivity with a low detection limit (LOD) of 0.007 mU/mL and a broad linear range from 0.01 to 1000 mU/mL. It was successfully applied to screen berberine hydrochloride as an AChE inhibitor. Crucially, the Colorisensor showed comparable accuracy to the standard Ellman's method and outperformed both traditional assays and emerging nanomaterial-based colorimetric methods by offering a wider detection range and a lower LOD.

Conclusion: This study presents a successful proof-of-concept for an integrated microneedle and nanozyme-based Colorisensor. The platform provides a viable and promising alternative pathway for the early diagnosis of neurodegenerative diseases and the screening of therapeutic drugs, highlighting its significant potential for point-of-care applications.

Background: Conventional intravesical chemotherapy for bladder cancer has shown limited clinical efficacy. To overcome this challenge, self-propelled nanomotors, including urease-modified nanomotors, have been developed. These nanomotors enhance drug diffusion in urine, offering advantages over traditional drugs and passive nanoparticles. However, a key issue remains: the inability to maintain long-term urease activity.

Methods: Nanozymes, glucose oxidase, and urease are synthesized into a three-enzyme nanomotors via biomineralization, serving as a power source. Cell membrane nanoparticles loaded with gemcitabine were combined with three-enzyme nanomotors to form dual-spherical nanomotors. TEM, DLS, and analyses of urease/glucose oxidase activity and nanomotor trajectories confirmed successful nanomotor fabrication. These nanomotors can regulate tumor cell glucose metabolism and release gemcitabine upon cellular entry, achieving a dual anticancer effect.

Results: Nanomotors synthesized through biomineralization methods exhibit the ability to retain long-term activity. After intravesical instillation, urease-containing nanomotors decomposed urea to produce carbon dioxide and ammonia, propelling rapid nanoparticle movement for deep bladder wall penetration. The homing ability of the tumor membrane-coated nanoparticles enhanced nanomotor accumulation in tumor cells. Subsequently, the nanomotors release Gox and gemcitabine, which significantly inhibit tumor progression.

Conclusion: This innovative strategy utilizes gemcitabine - loaded nanomotors to penetrate the mucus layer and target tumors, inducing cell death for the treatment of bladder cancer.

Ocular diseases represent a major and increasing public health concern. Although current treatment options are available, the management of complex cases, such as corneal diseases, diabetic retinopathy, glaucoma, age-related macular degeneration, and uveitis, remains inadequate. Recent studies have demonstrated that mesenchymal stem cell-derived exosomes (MSC-Exos), obtained from bone marrow, adipose tissue, and umbilical cord, have emerged as a promising cell-free therapeutic platform for various ocular diseases. These nanovesicles can be delivered via systems such as topical eye drops and intravitreal injection, targeting ocular tissues to exert anti-inflammatory, anti-apoptotic, and tissue-repairing effects. This review systematically synthesizes recent advances and the molecular mechanisms underlying the use of MSC-Exos in treating ocular diseases. Moreover, it provides an in-depth discussion of the challenges in the clinical application of MSC-Exos in ophthalmology, including standardized production, dosage optimization, delivery system improvement, and targeting enhancement, and proposes engineered targeting strategies based on surface modification and carrier optimization. Overall, this work establishes a rigorous framework for advancing MSC-Exos from experimental models to clinical implementation, offering novel therapeutic strategies through these innovative biopharmaceuticals for previously untreatable ocular conditions.

Breast cancer (BC) is the most common malignant tumor in women. Docetaxel (DTX), a chemotherapeutic agent derived from paclitaxel (PTX), has received approval from the US Food and Drug Administration (FDA) for the treatment of BC and various other malignancies. Nevertheless, its utility in clinical settings is constrained due to its poor water solubility and low oral bioavailability, dose-dependent toxicity, and a short systemic circulation half-life. Developing nano-drug delivery systems for DTX represents a well-established strategy to overcome these limitations. This review, based on a literature search of the PubMed database from 2019 to 2024 using the keywords "docetaxel", "breast cancer", and "nano-drug delivery system", summarises recent advances in targeted nanomedicine delivery systems for DTX and their application in BC treatment when combined with other delivery therapies. Nano-drug delivery systems encompass passive targeting (such as: nanomicelles, liposomes), active targeting (such as: G protein-coupled oestrogen receptor, integrin protein receptor), physicochemical targeting (such as: magnetic-responsive, temperature-responsive), and combined delivery (such as: photothermal therapy, chemotherapeutic drugs, and active components of traditional Chinese medicine). These systems hold great promise for enhancing DTX bioavailability, improving tumor targeting, and regulating drug release. Furthermore, key challenges limiting clinical translation are analysed. This paper provides a theoretical foundation and practical guidance for rationally designing DTX nanomedicines, accelerating their transition from laboratory research to clinical application and offering new hope for BC treatment.