International Journal of Nanomedicine最新文献

Background: Large-diameter titanium dioxide nanotubes (TNTs) have shown promise in preserving osteoblast function under oxidative stress (OS) in vitro. However, their ability to enhance osteogenesis in vivo under OS conditions and the underlying mechanisms remain unclear.

Purpose: This study aimed to evaluate the osteogenic potential of 110 nm TNTs (TNT110) compared to 30 nm TNTs (TNT30) in an aging rat model exhibiting OS, and to investigate the mechanisms involved.

Methods: Surface properties of TNTs were characterized, and in vitro and in vivo experiments were conducted to assess their osteoinductive effects under OS. Transcriptomic, proteomic analyses, and Western blotting were performed to investigate the protective mechanisms of TNT110 on osteoblasts. Protein adsorption studies focused on the roles of fibronectin (FN) and albumin (BSA) in modulating osteoblast behavior on TNT110.

Results: In both in vitro and in vivo experiments, TNT110 significantly improved new bone formation and supported osteoblast survival under OS conditions. Subsequent ribonucleic acid sequencing results indicated that TNT110 tended to attenuate inflammatory responses and reactive oxygen species (ROS) expression while promoting endoplasmic reticulum (ER) stress and extracellular matrix receptor interactions, all of which are crucial for osteoblast survival and functionality. Further confirmation indicated that the cellular behavior changes of osteoblasts in the TNT110 group could only occur in the presence of serum. Moreover, proteomic analysis under OS conditions revealed the pivotal roles of FN and BSA in augmenting TNT110's resistance to OS. Surface pretreatment of TNT110 with FN/BSA alone could beneficially influence the early adhesion, spreading, ER activity, and ROS expression of osteoblasts, a trend not observed with TNT30.

Conclusion: TNT110 effectively protects osteoblast function in the OS microenvironment by modulating protein adsorption, with FN and BSA synergistically enhancing osteogenesis. These findings suggest TNT110's potential for use in implants for elderly patients.

Oral squamous cell carcinoma (OSCC) is the most prevalent and deadly malignancy of the head and neck. The standard treatments for OSCC are surgery, radiotherapy, and chemoradiotherapy, which can cause severe cosmetic and functional damage to the oral cavity and impair the patients' quality of life. Photodynamic therapy (PDT) is a promising alternative that uses light-activated photosensitizers to induce selective phototoxicity and necrosis in the target tissues. PDT has several advantages over conventional treatments, such as minimal invasion, low side effects, high selectivity and preservation of the oral function and appearance. This review explores the principles, mechanisms, and current applications of PDT for OSCC. We address the challenges, such as the depth of light penetration and tissue hypoxia, and underscore the progressive innovations in photosensitizer enhancement, nanotechnological integration, and precision therapy. The exploration of biomarkers for refining patient selection and tailoring individualized treatment regimens is also undertaken. PDT holds promise as a secure and efficacious modality for OSCC management. Nonetheless, additional investigation is imperative to refine treatment protocols and validate sustained therapeutic success.

Hydrogels are multifunctional platforms. Through reasonable structure and function design, they use material engineering to adjust their physical and chemical properties, such as pore size, microstructure, degradability, stimulus-response characteristics, etc. and have a variety of biomedical applications. Hydrogel three-dimensional (3D) printing has emerged as a promising technique for the precise deposition of cell-laden biomaterials, enabling the fabrication of intricate 3D structures such as artificial vertebrae and intervertebral discs (IVDs). Despite being in the early stages, 3D printing techniques have shown great potential in the field of regenerative medicine for the fabrication of various transplantable tissues within the human body. Currently, the utilization of engineered hydrogels as carriers or scaffolds for treating intervertebral disc degeneration (IVDD) presents numerous challenges. However, it remains an indispensable multifunctional manufacturing technology that is imperative in addressing the escalating issue of IVDD. Moreover, it holds the potential to serve as a micron-scale platform for a diverse range of applications. This review primarily concentrates on emerging treatment strategies for IVDD, providing an in-depth analysis of their merits and drawbacks, as well as the challenges that need to be addressed. Furthermore, it extensively explores the biological properties of hydrogels and various nanoscale biomaterial inks, compares different prevalent manufacturing processes utilized in 3D printing, and thoroughly examines the potential clinical applications and prospects of integrating 3D printing technology with hydrogels.

Epigenetic dysregulation can significantly trigger the onset and progression of various diseases, epigenetic therapy is a new treatment strategy by changing DNA methylation, histone modification, N6-methyladenosine, chromatin modification and other epigenetic modifications to regulate gene expression levels for therapeutic purposes. However, small-molecule epigenetic drugs face challenges in disease treatment, such as lack of selectivity, limited therapeutic efficacy, and insufficient safety. Nanomedicine delivery systems offer significant advantages in addressing these issues by enhancing drug targeting, improving bioavailability, and reducing nonspecific distribution. This help minimize side effects while increasing both therapeutic effectiveness and safety of epigenetic drugs. In this review, we focus on the mechanism and role of epigenetic regulatory factors in diseases, as well as the challenges faced by small molecule inhibitors in treatment strategies, especially the research advancements in epigenetic drug delivery systems, review and discuss the therapeutic potential and challenges of using nanotechnology to develop epigenetic drug delivery systems.

Recanalization therapy can significantly improve the prognosis of patients with acute myocardial infarction (AMI). However, infarction or reperfusion-induced cardiomyocyte death, immune cell infiltration, fibroblast proliferation, and scarring formation lead to cardiac remodeling and gradually progress to heart failure or arrhythmia, resulting in a high mortality rate. Due to the inability of cardiomyocytes to regenerate, the healing of infarcted myocardium mainly relies on the formation of scars. Cardiac fibroblasts, as the main effector cells involved in repair and scar formation, play a crucial role in maintaining the structural integrity of the heart after MI. Recent studies have revealed that exosome-mediated intercellular communication plays a huge role in myocardial repair and signaling transduction after myocardial infarction (MI). Exosomes can regulate the biological behavior of fibroblasts by activating or inhibiting the intracellular signaling pathways through their contents, which are derived from cardiomyocytes, immune cells, endothelial cells, mesenchymal cells, and others. Understanding the interactions between fibroblasts and other cell types during cardiac remodeling will be the key to breakthrough therapies. This review examines the role of exosomes from different sources in the repair process after MI injury, especially the impacts on fibroblasts during myocardial remodeling, and explores the use of exosomes in the treatment of myocardial remodeling after MI.

Background: The challenge in treating irreversible nerve tissue damage has resulted in suboptimal outcomes for spinal cord injuries (SCI), underscoring the critical need for innovative treatment strategies to offer hope to patients.

Methods: In this study, gelatin methacrylic acid hydrogel scaffolds loaded with nerve growth factors (GMNF) were prepared and used to verify the performance of SCI. The physicochemical and biological properties of the GMNF were tested. The effect of GMNF on activity of neuronal progenitor cells (NPCs) was investigated in vitro. Histological staining and motor ability was carried out to assess the ability of SCI repair in SCI animal models.

Results: Achieving nerve growth factors sustained release, GMNF had good biocompatibility and could effectively penetrate into the cells with good targeting permeability. GMNF could better enhance the activity of NPCs and promote their directional differentiation into mature neuronal cells in vitro, which could exert a good neural repair function. In vivo, SCI mice treated with GMNF recovered their motor abilities more effectively and showed better wound healing by macroscopic observation of the coronal surface of their SCI area. Meanwhile, the immunohistochemistry demonstrated that the GMNF scaffolds effectively promoted SCI repair by better promoting the colonization and proliferation of neural stem cells (NSCs) in the SCI region and targeted differentiation into mature neurons.

Conclusion: The application of GMNF composite scaffolds shows great potential in SCI treatment, which are anticipated to be a potential therapeutic bioactive material for clinical application in repairing SCI in the future.

Background: The skin regulates body processes. When damaged, it is prone to breeding bacteria, causing inflammation and impeding wound healing. There is an urgent need for new dressings that can combat bacteria to aid in infectious wound repair.

Methods: In this study, a curcumin-loaded nanocomposite hydrogel dressing (GelMA/AHA-Gel@Cur) with antibacterial properties and strong toughness was synthesized, designed to combine the modified gelatin-based hydrogel (GelMA/AHA) with curcumin-coated gelatin (Gel@Cur) nanoparticles to promote the healing of bacterial infection wounds. Under UV irradiation, methylacrylylated gelatin (GelMA) and aldehyaluronic acid (AHA) formed a composite network hydrogel through radical polymerization and Schiff base reaction. Meanwhile, the residual aldehyde group on the molecular chain of AHA securely locked Gel@Cur nanoparticles in the hydrogel network through Schiff base reaction.

Results: The addition of Gel@Cur nanoparticles not only enhanced the hydrogel's mechanical strength but also facilitated a sustained, gradual release of curcumin, endowing the composite hydrogel with robust antimicrobial capabilities. In an animal model of infected wounds, the composite hydrogel significantly improved wound closure, healing, and vascularization compared to the control group. Hemocompatibility tests confirmed the hydrogel's safety, with a hemolysis ratio of just 0.45%. Histological evaluation following treatment with the composite hydrogel showed improved tissue architecture, increased collagen deposition, and regeneration of dermal gland structures.

Conclusion: The GelMA/AHA-Gel@Cur composite hydrogel exhibits excellent mechanical properties, potent antimicrobial activity, and controlled drug release, along with superior cell and hemocompatibility. These characteristics make it a promising material for infected wound repair and a potential candidate for clinical skin regeneration applications.

Purpose: Acute alcohol intoxication (AAI) is a life-threatening medical condition resulting from excessive alcohol consumption. Our research revealed the potential of morin (MOR) in treating AAI. However, MOR's effectiveness against AAI was hindered by its poor solubility in water and low bioavailability. In this study, our aim was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance MOR's solubility and bioavailability, evaluate its anti-AAI effects, and investigate the underlying mechanism.

Methods: The composition of MOR-loaded self-nanoemulsifying drug delivery system (MOR-SNEDDS) was determined by constructing pseudo-ternary phase diagrams, and its formulation proportion was optimized using the Box-Behnken design. Following characterization of MOR-SNEDDS, we investigated its pharmacokinetics and biodistribution in healthy animals. Additionally, we assessed the anti-AAI effects and gastric mucosal protection of MOR-SNEDDS in an AAI mice model, exploring potential mechanisms.

Results: After breaking down into tiny droplets, the optimized mixture of MOR-SNEDDS showed small droplet size on average, even distribution, strong stability, and permeability. Pharmacokinetic studies indicated that MOR-SNEDDS, compared to a MOR suspension, increased the area under the plasma concentration-time curve (AUC_0-t) by 10.43 times. Additionally, studies on how drugs move and are distributed in the body showed that MOR-SNEDDS had an advantage in passively targeting the liver. Moreover, in a mouse model for alcohol addiction, MOR not only decreased alcohol levels by boosting the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the stomach and liver, which counteracted the loss of righting reflex (LORR), but also reduced alcohol-induced damage to the stomach lining by lowering malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) levels. Furthermore, MOR-SNEDDS notably amplified these effects.

Conclusion: MOR exhibits significant potential as a new medication for treating AAI, and utilizing MOR-SNEDDS with high oral bioavailability represents a promising new strategy in combating AAI.

Background: Cinobufagin, the primary active compound in toad venom, is commonly used for anti-tumor, anti-inflammatory, and analgesic purposes. However, its specific bone-protective effects remain uncertain. This research aims to ascertain the bone-protective properties of cinobufagin and investigate underlying mechanisms.

Methods: Mice were ovariectomized to establish an osteoporosis model, followed by intraperitoneal injections of cinobufagin and cinobufagin-treated RAW.264.7-derived exosomes for therapy. MicroCT, HE staining, and TRAP staining were employed to evaluate bone mass and therapeutic outcomes, while mRNA sequencing and immunoblotting were utilized to assess markers of bone metabolism, inflammation, and lipid peroxidation. Osteoblast and osteoclast precursor cells were differentiated to observe the impact of cinobufagin-treated exosomes derived from RAW264.7 cells on bone metabolism. Exosomes characteristics were studied using transmission electron microscopy and particle size analysis, and miRNA binding targets in exosomes were determined by luciferase reporting.

Results: In ovariectomized mice, cinobufagin and cinobufagin-treated exosomes from RAW264.7 cells increased trabecular bone density and mass in the femur, while also decreasing inflammation and lipid peroxidation. The effect was reversed by an exosomes inhibitor. In vitro experiments revealed that cinobufagin-treated exosomes from RAW264.7 cells enhanced osteogenic and suppressed osteoclast differentiation, possibly linked to Upregulated miR-3102-5p in RAW-derived exosomes. MiR-3102-5p targets the 3'UTR region of alox15, thereby suppressing its expression and reducing the lipid peroxidation process in osteoblasts.

Conclusion: Overall, this study clarified cinobufagin's bone-protective effects and revealed that cinobufagin can enhance the delivery of miR-3102-5p targeting alox15 through macrophage-derived exosomes, demonstrating anti-lipid peroxidation and anti-inflammatory effects.

Background: Phototherapy based on photocatalytic semiconductor nanomaterials has received considerable attention for the cancer treatment. Nonetheless, intense efficacy for in vivo treatment is restricted by inadequate photocatalytic activity and visible light response.

Methods: In this study, we designed a photocatalytic heterostructure using graphitic carbon nitride (g-C₃N₄) and tin disulfide (SnS₂) to synthesize g-C₃N₄/SnS₂ heterostructure through hydrothermal process. Furthermore, Au nanoparticles were decorated in situ deposition on the surface of the g-C₃N₄/SnS₂ heterostructure to form g-C₃N₄/SnS₂@Au nanoparticles.

Results: The g-C₃N₄/SnS₂@Au nanoparticles generated intense reactive oxygen species radicals under near-infrared (NIR) laser irradiation through photodynamic therapy (PDT) pathways (Type-I and Type-II). These nanoparticles exhibited enhanced photothermal therapy (PTT) efficacy with high photothermal conversion efficiency (41%) when subjected to 808 nm laser light, owing to the presence of Au nanoparticles. The in vitro studies have indicated that these nanoparticles can induce human liver carcinoma cancer cell (HepG2) apoptosis (approximately 80% cell death) through the synergistic therapeutic effects of PDT and PTT. The in vivo results demonstrated that these nanoparticles exhibited enhanced efficient antitumor effects based on the combined effects of PDT and PTT.

Conclusion: The g-C₃N₄/SnS₂@Au nanoparticles possessed enhanced photothermal properties and PDT effect, good biocompatibility and intense antitumor efficacy. Therefore, these nanoparticles could be considered promising candidates through synergistic PDT/PTT effects upon irradiation with NIR laser for cancer treatment.