Search Results (45)

Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by overcoming these limitations through targeted drug delivery and enhanced therapeutic precision. This review examines key nanotechnological strategies in obesity management, including targeting white adipose tissue (WAT) and the vascular marker prohibitin, promoting WAT browning, and utilizing photothermal therapy and magnetic hyperthermia as nanotheranostic tools. We discuss major nanomedicine platforms—such as liposomes, nanoemulsions, and polymeric nanoparticles—alongside emerging applications in gene nanotherapy and herbal formulations. Potential toxicity concerns are also addressed. In summary, nanomedicine holds substantial potential to revolutionize obesity treatment through targeted, effective, and multifunctional therapeutic strategies. Full article

Diabetic wounds, as one of the most challenging complications of diabetes, exhibit impaired healing due to hyperglycemia, infection, vascular damage, microvascular deficits, dysregulated immune responses, and neuropathy. Conventional treatments are often limited by low drug bioavailability, transient therapeutic effects, and insufficient synergy across multiple pathways. Natural bioactive compounds are potential alternatives due to their multifunctional properties, including antioxidant, antimicrobial, and proangiogenic activities; however, their application is constrained by poor water solubility and rapid metabolism. Their integration with natural or synthetic nanovehicles significantly enhances stability, targeting, and controlled-release capabilities, while enhancing synergistic antimicrobial, immunomodulatory, and pro-repair functions. This review systematically catalogs the application of nanomaterial-loaded biomolecules, focuses on innovative progress in plant-based and animal-derived nanosystems, and further elucidates the multimodal therapeutic potential of synthetic–natural hybrid nanosystems. By synthesizing cutting-edge research, we also summarize advantageous features, development prospects, and existing challenges from the three dimensions of mechanistic evidence, preclinical validation, and current nanodelivery platforms, and propose a framework for grading application potential to provide a theoretical basis and strategic guidance for the rational design and clinical translation of future nanomedicines. Full article

Matrix metalloproteinase-9 (MMP-9) is implicated in tumor progression and vascular diseases, contributing to angiogenesis, metastasis, and extracellular matrix degradation. This review comprehensively examines the relationship between MMP-9 and these pathologies, exploring the underlying molecular mechanisms and signaling pathways involved. Specifically, we discuss the contribution of MMP-9 to tumor epithelial–mesenchymal transition, angiogenesis, and metastasis, as well as its involvement in a spectrum of vascular diseases, including macrovascular, cerebrovascular, and ocular vascular diseases. This review focuses on recent advances in MMP-9-targeted nanomedicine strategies, highlighting the design and application of responsive nanoparticles for enhanced drug delivery. These nanotherapeutic strategies leverage MMP-9 overexpression to achieve targeted drug release, improved tumor penetration, and reduced systemic toxicity. We explore various nanoparticle platforms, such as liposomes and polymer nanoparticles, and discuss their mechanisms of action, including degradation, drug release, and targeting specificity. Finally, we address the challenges posed by the heterogeneity of MMP-9 expression and their implications for personalized therapies. Ultimately, this review underscores the diagnostic and therapeutic potential of MMP-9-targeted nanomedicines against tumors and vascular diseases. Full article

The Enhanced Permeability and Retention (EPR) effect is a key mechanism for passive tumor targeting, which involves the selective accumulation of therapeutic nanoparticles in tumors due to their unique vascular characteristics. While previous reviews have explored this phenomenon, the present review offers a comprehensive, multidisciplinary approach, highlighting recent advancements in strategies to enhance the EPR effect, as well as novel insights into the role of tumor microenvironment heterogeneity and the multifaceted approaches to overcome EPR-related challenges. This review provides a detailed analysis of the latest developments in nanocarriers’ design, including size, shape, and surface modifications, as well as cutting-edge multi-stage drug delivery systems. Furthermore, the integration of physical, pharmacological, and combinatory therapies to optimize the EPR effect is also discussed, aiming to improve the clinical translation of nanomedicines. Unlike other reviews, this work emphasizes the dynamic interaction between the tumor microenvironment and the vascular network, which remains underexplored in the current literature. In addition, specific clinical trials’ outcomes are highlighted and future directions to address existing limitations are proposed, offering a clearer roadmap regarding clinical applications in cancer therapy. Full article

Reductive stress (RS), characterized by excessive accumulation of reducing equivalents such as NADH and NADPH, is emerging as a key factor in metabolic disorders and cancer. While oxidative stress (OS) has been widely studied, RS and its complex interplay with endocrine regulation remain less understood. This review explores molecular circuits of bidirectional crosstalk between metabolic hormones and RS, focusing on their role in diabetes, obesity, cardiovascular diseases, and cancer. RS disrupts insulin secretion and signaling, exacerbates metabolic inflammation, and contributes to adipose tissue dysfunction, ultimately promoting insulin resistance. In cardiovascular diseases, RS alters vascular smooth muscle cell function and myocardial metabolism, influencing ischemia-reperfusion injury outcomes. In cancer, RS plays a dual role: it enhances tumor survival by buffering OS and promoting metabolic reprogramming, yet excessive RS can trigger proteotoxicity and mitochondrial dysfunction, leading to apoptosis. Recent studies have identified RS-targeting strategies, including redox-modulating therapies, nanomedicine, and drug repurposing, offering potential for novel treatments. However, challenges remain, particularly in distinguishing physiological RS from pathological conditions and in overcoming therapy-induced resistance. Future research should focus on developing selective RS biomarkers, optimizing therapeutic interventions, and exploring the role of RS in immune and endocrine regulation. Full article

Age-related macular degeneration (AMD) is a predominant cause of vision loss, posing significant challenges in its management despite advancements such as anti-vascular endothelial growth factor (anti-VEGF) therapy. Nanomedicine, with its novel properties and capabilities, offers promising potential to transform the treatment paradigm for AMD. This review reports the significant advancements in the use of diverse nanoparticles (NPs) for AMD in vitro, in vivo, and ex vivo, including liposomes, lipid nanoparticles, nanoceria, nanofibers, magnetic nanoparticles, quantum dots, dendrimers, and polymer nanoparticles delivered in forms such as gels, eye drops, intravitreally, or intravenously. Drug delivery was the most common use of NPs for AMD, followed by photodynamic therapy dose enhancement, antioxidant function for nanoceria, biomimetic activity, and immune modulation. Innovative approaches arising included nanotechnology-based photodynamic therapy and light-responsive nanoparticles for controlled drug release, as well as gene therapy transfer. Nanomedicine offers a transformative approach to the treatment and management of AMD, with diverse applications. The integration of nanotechnology in AMD management not only provides innovative solutions to overcome current therapeutic limitations but also shows potential in enhancing outcomes and patient quality of life. Full article

Background and Objectives: Ischemia-reperfusion (I/R) injury is a process in which impaired perfusion is restored by restoring blood flow and tissue recirculation. Nanomedicine uses cutting-edge technologies that emerge from interdisciplinary influences. In the literature, there are very few in vivo and in vitro studies on how cerium oxide (CeO₂) affects systemic anti-inflammatory response and inflammation. Therefore, in our study, we aimed to investigate whether CeO₂ administration has a protective effect against myocardial I/R injury in the liver and kidneys. Materials and Methods: Twenty-four rats were randomly divided into four groups after obtaining approval from an ethics committee. A control (group C), cerium oxide (group CO), IR (group IR), and Cerium oxide-IR (CO-IR group) groups were formed. Intraperitoneal CeO₂ was administered at a dose of 0.5 mg/kg 30 min before left thoracotomy and left main coronary (LAD) ligation, and myocardial muscle ischemia was induced for 30 min. After LAD ligation was removed, reperfusion was performed for 120 min. All rats were euthanized using ketamine, and blood was collected. Liver and kidney tissue samples were evaluated histopathologically. Serum AST (aspartate aminotransferase), ALT (alanine aminotransaminase), GGT (gamma-glutamyl transferase), glucose, TOS (Total Oxidant Status), and TAS (Total Antioxidant Status) levels were also measured. Results: Necrotic cell and mononuclear cell infiltration in the liver parenchyma of rats in the IR group was observed to be significantly increased compared to the other groups. Hepatocyte degeneration was greater in the IR group compared to groups C and CO. Vascular vacuolization and hypertrophy, tubular degeneration, and necrosis were increased in the kidney tissue of the IR group compared to the other groups. Tubular dilatation was significantly higher in the IR group than in the C and CO groups. TOS was significantly higher in all groups than in the IR group (p < 0.0001, p < 0.0001, and p = 0.006, respectively). However, TAS level was lower in the IR group than in the other groups (p = 0.002, p = 0.020, and p = 0.031, respectively). Renal and liver histopathological findings decreased significantly in the CO-IR group compared to the IR group. A decrease in the TOS level and an increase in the TAS level were found compared to the IR group. The AST, ALT, GGT, and Glucose levels are shown. Conclusions: CeO₂ administered before ischemia-reperfusion reduced oxidative stress and ameliorated IR-induced damage in distant organs. We suggest that CeO₂ exerts protective effects in the myocardial IR model. Full article

Background/Objectives: The key components of the blood–brain barrier (BBB) are endothelial cells, pericytes, astrocytes, and the capillary basement membrane. The BBB serves as the main barrier for drug delivery to the brain and is the most restrictive endothelial barrier in the body. Nearly all large therapeutic molecules and over 90% of small-molecule drugs cannot cross the BBB. To overcome this challenge, nanotechnology, particularly drug delivery systems such as nanoparticles (NPs), have gained significant attention. Methods: Poly(lactide-co-glycolide) (PLGA) and albumin-based NPs (bovine/human), with or without transferrin (Tf) ligands (BSA, HSA, BSA-Tf, HSA-Tf), and nanolipid carriers (NLC) were synthesized. The interactions of these NPs with human brain microvascular endothelial cells (hBMECs), human brain vascular pericytes (hBVPs), and human astrocytes (hASTROs) were analyzed. Results: At doses of 15.62 µg/mL, 31.25 µg/mL, and 62.5 µg/mL, none of the NPs caused toxic effects on hBMECs, hBVPs, or hASTROs after 3 h of incubation. All NPs were internalized by the cells, but BSA-Tf and HSA-Tf showed significantly higher uptake in hBMECs in a dose-dependent manner. Ultrastructural analysis revealed notable differences between NP formulation and cell type. Conclusions: Our findings underscore the potential of ligand-targeted NPs to selectively interact with BBB endothelial cells. Ultrastructural analysis reveals distinct cellular processing pathways for various NP formulations across BBB-associated cell types, with autophagy emerging as a crucial mechanism for NP handling in pericytes and astrocytes. Changes in NP chemical properties upon biological exposure present significant challenges for nanomedicine design, emphasizing the need for further investigation into NP interactions at the cellular and subcellular levels. Full article

Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-EVs) are valuable in nanomedicine as natural nanocarriers, carrying information molecules from their parent cells and fusing with targeted cells. miRNA-126, specific to endothelial cells and derived from these vesicles, supports vascular integrity and angiogenesis and has protective effects in kidney diseases. Objective: This study investigates the delivery of miRNA-126 and anti-miRNA-126 via UC-EVs as natural nanocarriers for treating nephrotoxic injury in vitro. Method: The umbilical cord-derived mesenchymal stem cell and UC-EVs were characterized according to specific guidelines. Rat kidney proximal tubular epithelial cells (tubular cells) were exposed to nephrotoxic injury through of gentamicin and simultaneously treated with UC-EVs carrying miRNA-126 or anti-miRNA-126. Specific molecules that manage cell cycle progression, proliferation cell assays, and newly synthesized DNA and DNA damage markers were evaluated. Results: We observed significant increases in the expression of cell cycle markers, including PCNA, p53, and p21, indicating a positive cell cycle regulation with newly synthesized DNA via BrDU. The treatments reduced the expression of DNA damage marker, such as H2Ax, suggesting a lower rate of cellular damage. Conclusions: The UC-EVs, acting as natural nanocarriers of miRNA-126 and anti-miRNA-126, offer nephroprotective effects in vitro. Additionally, other components in UC-EVs, such as proteins, lipids, and various RNAs, might also contribute to these effects. Full article

This review article explores the fundamental role of receptor targeting in overcoming drug resistance in cancer therapy, an area of critical concern given the persistently high rates of cancer morbidity and mortality globally. We highlight how receptor biology intersects with the development of therapeutic resistance with a specific focus on anti-angiogenic agents, immune checkpoint inhibitors, and monoclonal antibodies, which directly or indirectly influence receptor pathways. We also explore how other receptor tyrosine kinases can initially suppress tumor growth, yet often lead to resistance, underscoring the need for novel combinatorial approaches that incorporate advanced receptor modulation techniques. Further, the review delves into the mechanisms by which modulation of the tumor microenvironment and immune system via receptor pathways can overcome resistance to traditional immunotherapies. Additionally, emerging technologies in receptor-targeted nanomedicine are also highlighted, showcasing their potential to revolutionize drug delivery and improve therapeutic outcomes by targeting specific receptor interactions. Ultimately, this review calls for a deeper understanding of receptor dynamics to develop more precise interventions, including insights from various healthcare settings that can prevent or circumvent drug resistance, thus enhancing patient outcomes in oncology. Full article

Recent advances in three-dimensional (3D) culturing and nanotechnology offer promising pathways to overcome the limitations of drug screening, particularly for tumors like neuroblastoma. In this study, we develop a high-throughput microfluidic chip that integrates a concentration gradient generator (CGG) with a 3D co-culture system, constructing the vascularized microenvironment in tumors by co-culturing neuroblastoma (SY5Y cell line) and human brain microvascular endothelial cells (HBMVECs) within a decellularized extracellular matrix (dECM) hydrogels. The automated platform enhances the simulation of the tumor microenvironment and allows for the precise control of the concentrations of nanomedicines, which is crucial for evaluating therapeutic efficacy. The findings demonstrate that the high-throughput platform can significantly accelerate drug discovery. It efficiently screens and analyzes drug interactions in a biologically relevant setting, potentially revolutionizing the drug screening process. Full article

Transient receptor potential (TRP) channels, first identified in Drosophila in 1969, are multifunctional ion channels expressed in various cell types. Structurally, TRP channels consist of six membrane segments and are classified into seven subfamilies. Transient receptor potential ankyrin 1 (TRPA1), the first member of the TRPA family, is a calcium ion affinity non-selective cation channel involved in sensory transduction and responds to odors, tastes, and chemicals. It also regulates temperature and responses to stimuli. Recent studies have linked TRPA1 to several disorders, including chronic pain, inflammatory diseases, allergies, and respiratory problems, owing to its activation by environmental toxins. Mutations in TRPA1 can affect the sensory nerves and microvasculature, potentially causing nerve pain and vascular problems. Understanding the function of TRPA1 is important for the development of treatments for these diseases. Recent developments in nanomedicines that target various ion channels, including TRPA1, have had a significant impact on disease treatment, providing innovative alternatives to traditional disease treatments by overcoming various adverse effects. Full article

Cardiovascular diseases (CVDs) pose a significant global health threat due to their complex pathogenesis and high incidence, imposing a substantial burden on global healthcare systems. Integrins, a group of heterodimers consisting of α and β subunits that are located on the cell membrane, have emerged as key players in mediating the occurrence and progression of CVDs by regulating the physiological activities of endothelial cells, vascular smooth muscle cells, platelets, fibroblasts, cardiomyocytes, and various immune cells. The crucial role of integrins in the progression of CVDs has valuable implications for targeted therapies. In this context, the development and application of various integrin antibodies and antagonists have been explored for antiplatelet therapy and anti-inflammatory-mediated tissue damage. Additionally, the rise of nanomedicine has enhanced the specificity and bioavailability of precision therapy targeting integrins. Nevertheless, the complexity of the pathogenesis of CVDs presents tremendous challenges for monoclonal targeted treatment. This paper reviews the mechanisms of integrins in the development of atherosclerosis, cardiac fibrosis, hypertension, and arrhythmias, which may pave the way for future innovations in the diagnosis and treatment of CVDs. Full article

Poor prognosis in high-grade gliomas is mainly due to fatal relapse after surgical resection in the absence of efficient chemotherapy, which is severely hampered by the blood–brain barrier. However, the leaky blood–brain–tumour barrier forms upon tumour growth and vascularization, allowing targeted nanocarrier-mediated drug delivery. The homotypic targeting ability of cell-membrane fragments obtained from cancer cells means that these fragments can be exploited to this aim. In this experimental work, injectable nanoemulsions, which have a long history of safe clinic usage, have been wrapped in glioma-cell membrane fragments via co-extrusion to give targeted, homogeneously sized, sterile formulations. These systems were then loaded with three different chemotherapeutics, in the form of hydrophobic ion pairs that can be released into the target site thanks to interactions with physiological components. The numerous assays performed in two-dimensional (2D) and three-dimensional (3D) cell models demonstrate that the proposed approach is a versatile drug-delivery platform with chemo-tactic properties towards glioma cells, with adhesive interactions between the target cell and the cell membrane fragments most likely being responsible for the effect. This approach’s promising translational perspectives towards personalized nanomedicine mean that further in vivo studies are foreseen for the future. Full article

Insufficient drug accumulation in tumors is still a major concern for using cancer nanotherapeutics. Here, the neutrophil-based delivery of three nanoparticle types—liposomes, PLGA, and magnetite nanoparticles—was assessed both in vitro and in vivo. Confocal microscopy and a flow cytometry analysis demonstrated that all the studied nanoparticles interacted with neutrophils from the peripheral blood of mice with 4T1 mammary adenocarcinoma without a significant impact on neutrophil viability or activation state. Intravital microscopy of the tumor microenvironment showed that the neutrophils did not engulf the liposomes after intravenous administration, but facilitated nanoparticle extravasation in tumors through micro- and macroleakages. PLGA accumulated along the vessel walls in the form of local clusters. Later, PLGA nanoparticle-loaded neutrophils were found to cross the vascular barrier and migrate towards the tumor core. The magnetite nanoparticles extravasated in tumors both via spontaneous macroleakages and on neutrophils. Overall, the specific type of nanoparticles largely determined their behavior in blood vessels and their neutrophil-mediated delivery to the tumor. Since neutrophils are the first to migrate to the site of inflammation, they can increase nanodrug delivery effectiveness for nanomedicine application. Full article