International Journal of Nanomedicine最新文献

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.

Objective: Radioimmunotherapy (RIT) is a promising treatment for deep-seated and metastatic tumors, but its efficacy is limited by the immunosuppressive tumor microenvironment (TME) and a narrow therapeutic window. This study aimed to develop a novel nanoplatform to overcome these constraints by simultaneously sensitizing tumors to radiation, inducing cuproptosis, and reprogramming the immunosuppressive TME.

Methods: We engineered a PEGylated copper-loaded black phosphorus nanoplatform (BPNS@Cu-PEG). Its functionality as a radiosensitizer and cuproptosis inducer was evaluated. The mechanisms of TME reprogramming were investigated, including glutathione (GSH) depletion, reactive oxygen species (ROS) amplification, hypoxia alleviation, and M2-to-M1 macrophage repolarization. Furthermore, we systematically evaluated its antitumor immune effects in vitro and in vivo.

Results: BPNS@Cu-PEG was synthesized with a high copper incorporation rate of 93%. In vitro cellular assays confirmed that the internalized nanoplatform effectively induced cuproptosis and immunogenic cell death (ICD) while simultaneously regulating the TME. In vivo, BPNS@Cu-PEG not only potently inhibited tumor progression and stimulated robust antitumor immunity under low-dose radiotherapy but also exhibited an excellent safety profile.

Conclusion: This work establishes a copper-based, low-dose radioimmunotherapy strategy. The BPNS@Cu-PEG nanoplatform presents a viable and potent strategy to counteract radioresistance and promote systemic antitumor immunity, potentially broadening the therapeutic application and safety profile of RIT.

Gliomas are the most prevalent Central Nervous System (CNS) tumors. Among them, glioblastoma (grade IV) is the most challenging brain cancer because of its highly aggressive nature, treatment resistance and poor prognosis. Matrix metalloproteinase (MMP) is a family of zinc-dependent protein hydrolases. In recent years, MMPs have become a research focus owing to their central role in tumor microenvironment remodeling, angiogenesis, invasion, metastasis. Clinical studies have shown that the expression levels of MMPs in glioma tissues exhibit a significant positive correlation with the degree of malignancy and aggressiveness of gliomas. Therefore, the idea of MMPs as a detection target and therapeutic target can be proposed. Nanoparticle drug delivery system, as a cutting-edge technology, has shown great potential and broad prospects in clinical applications. The system realizes the targeted delivery, sustained-release control and bioavailability of drugs, and provides new ideas and means for the management of various pathological conditions. In this review, we will comprehensively discuss the expression relationship and major regulatory mechanisms between MMPs and gliomas, the composition of nano-drug delivery systems, routes of administration, and common types of nanomaterials used for the treatment of gliomas. In addition, we focus on cell-penetrating peptides (CPPs) as an entry point. We summarize the common kinds of activatable CPPs and how they are applied in nano-drug delivery systems. It is also found that MMP-responsive systems, which can be used for the treatment of gliomas, can activate CPPs, and through the synergistic effect between CPPs and MMPs, MMPs can be used as detection or therapeutic targets and combined with nano-drug delivery system for the medical management of gliomas. The nano-drug delivery system can demonstrate exceptional blood-brain barrier (BBB) penetration efficiency and precisely target the glioma region to release the drug. This delivery approach may prove to be beneficial for glioma patients.

This review highlights the potential of muco-adhesive hydrogel-based exosome delivery vehicles for the regeneration of periodontal tissue and the reduction of inflammation in periodontitis. Exosomes, mainly produced from mesenchymal stem cells (MSCs), represent nano-sized vesicles loaded with bioactive molecules that can stimulate tissue repair and modulate inflammatory pathways. The review provides a thorough view for the synthesis of the in vitro, in vivo and clinical-pilot studies on exosome-loaded muco-adhesive hydrogels, encompassing the physicochemical characterization, exosome delivery and biological efficacies. In vitro studies highlight the regenerative potential of exosomes on periodontal ligament cells and on alveolar bone cells. In vivo animal models have shown significant improvements in tissue regeneration with effective inflammation control. Preliminary clinical pilot studies similarly show promising results for periodontal tissue healing. The use of exons in combination with muco-adhesive hydrogels provides an effective and non-invasive approach for the targeted, prolonged therapeutic delivery for the treatment of periodontal disease. The main conclusion of this review is that exosome loaded muco-adhesive hydrogels represent a promising strategy for developing strategies to treat periodontitis, setting up as its double aims to enhance the regeneration of tissues and reduce inflammation.

Neutrophils, a key component of the innate immune system, play a crucial role in immune responses. In 2004, Brinkmann et al identified neutrophil extracellular traps (NETs) as a novel antibacterial mechanism. However, NETs have since been implicated in the pathogenesis of various diseases, including autoimmune disorders, sepsis, and cancer. Consequently, targeting NETs has emerged as a promising therapeutic approach. Mesenchymal stem cells (MSCs) have demonstrated efficacy in modulating NET formation, but MSC-derived exosomes offer distinct advantages over whole MSCs due to their lower immunogenicity, higher biological stability, and ability to deliver bioactive molecules like miRNAs and CD59. These exosomes can block critical signaling pathways involved in NET formation and protect neutrophil mitochondria, inhibiting NET release. Despite challenges such as low yield and targeting efficiency, ongoing research has made significant strides in addressing these issues. This article reviews the current progress in MSC-derived exosome-based anti-NET therapies and discusses potential strategies to enhance their therapeutic application.

Osteoporosis (OP) is a common bone disease that involves low bone mass and high risk of fracture mainly in older men and women and perimenopausal years. Although conventional therapies provide good therapeutic effects, they have numerous limitations, including poorly targeted and systemic administration and severe side effects. Recent developments in nanotechnology enabled design of enzyme-immobilized nanocarriers as experimental platforms to enhance the delivery of therapeutic agents to bone tissue. This review pays special attention to the development of these multifunctional systems that can transport anti-osteoporotic agents and carry enzymes to stimulate bone formation. Enzymes like alkaline phosphatase for mineralization, superoxide dismutase for reactive oxygen species reduction, and cathepsin K inhibitors for osteoclast regulation are highlighted to demonstrate rationale behind enzyme immobilization. Enzyme immobilization promotes local bone regeneration by increasing enzyme stability and activity at target site offering more sustained therapeutic effect in OP therapy. Polymeric NP and liposomes like nanocarriers are well explained along with their various mechanisms such as stability, bioavailability controlling and release kinetics. Further, we review the current literature for the recent in vivo and in vitro studies highlighting the potential of these systems in stimulating osteoblast function and suppressing osteoclast-mediated bone resorption. Areas for future research include improving carrier design for increased targetability and exploring the clinical translation of these nanocarrier systems for OP management.

With the ongoing trend of population aging worldwide, the incidence of Alzheimer's disease (AD) is steadily increasing. In the absence of effective therapeutic options for atypical forms of AD, reducing its prevalence and improving treatment outcomes have become pressing priorities. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have attracted growing attention as a new cell-free therapeutic approach for AD due to their high stability, low immunogenicity, and minimal tumorigenic risk. This review provides a comprehensive overview of the pathological mechanisms underlying AD, highlights the diagnostic potential of MSC-EVs, and elaborates on their therapeutic advantages and mechanisms of action. Furthermore, it addresses the key challenges and considerations associated with the clinical translation of MSC-EVs.