Search Results (5,167)

Background and Objectives: Over the past few years, there has been a significant shift in focus from developing better diagnostic tools to detecting Alzheimer’s disease (AD) earlier and initiating treatment interventions. This review will explore four main objectives: (a) the role of biomarkers in enhancing the diagnostic accuracy of AD, highlighting the major strides that have been made in recent years; (b) the role of neuropsychological testing in identifying biomarkers of AD, including the relationship between cognitive performance and neuroimaging biomarkers; (c) the amyloid hypothesis and possible molecular mechanisms of AD; and (d) the innovative AD therapeutics and the challenges and limitations of AD research. Materials and Methods: We have searched PubMed and Scopus databases for peer-reviewed research articles published in English (preclinical and clinical studies as well as relevant reviews and meta-analyses) investigating the molecular mechanisms, biomarkers, and treatments of AD. Results: Genome-wide association studies (GWASs) discovered 37 loci associated with AD risk. Core 1 biomarkers (α-amyloid Aβ42, phosphorylated tau, and amyloid PET) detect early AD phases, identifying both symptomatic and asymptomatic individuals, while core 2 biomarkers inform the short-term progression risk in individuals without symptoms. The recurrent failures of Aβ-targeted clinical studies undermine the amyloid cascade hypothesis and the objectives of AD medication development. The molecular mechanisms of AD include the accumulation of amyloid plaques and tau protein, vascular dysfunction, neuroinflammation, oxidative stress, and lipid metabolism dysregulation. Significant advancements in drug delivery technologies, such as focused Low-Ultrasound Stem, T cells, exosomes, nanoparticles, transferin, nicotinic and acetylcholine receptors, and glutathione transporters, are aimed at overcoming the BBB to enhance treatment efficacy for AD. Aducanumab and Lecanemab are IgG1 monoclonal antibodies that retard the progression of AD. BACE inhibitors have been explored as a therapeutic strategy for AD. Gene therapies targeting APOE using the CRISPR/Cas9 genome-editing system are another therapeutic avenue. Conclusions: Classic neurodegenerative biomarkers have emerged as powerful tools for enhancing the diagnostic accuracy of AD. Despite the supporting evidence, the amyloid hypothesis has several unresolved issues. Novel monoclonal antibodies may halt the AD course. Advances in delivery systems across the BBB are promising for the efficacy of AD treatments. Full article

Background/Objectives: Antibody–drug conjugates are a rapidly evolving class of cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs. This review explores experimental and computational advances in ADC design, focusing on structural elements and optimization strategies. Methods: We examined recent developments in the mechanisms of action, antibody engineering, linker chemistries, and payload selection. Emphasis was placed on experimental strategies and computational tools, including molecular modeling and AI-driven structure prediction. Results: ADCs function through both internalization-dependent and -independent mechanisms, enabling targeted drug delivery and bystander effects. The therapeutic efficacy of ADCs depends on key factors: antigen specificity, linker stability, and payload potency. Linkers are categorized as cleavable or non-cleavable, each with distinct advantages. Payloads—mainly tubulin inhibitors and DNA-damaging agents—require extreme potency to be effective. Computational methods have become essential for antibody modeling, developability assessment, and in silico optimization of ADC components, accelerating candidate selection and reducing experimental labor. Conclusions: The integration of experimental and in silico approaches enhances ADC design by improving selectivity, stability, and efficacy. These strategies are critical for advancing next-generation ADCs with broader applicability and improved therapeutic indices. Full article

Numerous studies on specific cannabis compounds (cannabinoids and phenolic acids) have demonstrated their therapeutic potential, with their administration methods remaining a key research focus. Transdermal drug delivery (TDD) systems are gaining attention due to their advantages, such as painless administration, controlled release, direct absorption into the bloodstream, and its ability to bypass hepatic metabolism. The thin films obtained via pulsed laser deposition consist of micro- and nanoparticles capable of migrating through skin pores upon contact. This study investigates the interaction of phenolic compounds in hemp seeds with pulsed laser beams. The main goal is to achieve the ablation and deposition of these compounds as thin films suitable for TDD applications. The other key objective is optimizing laser energy to enhance the industrial feasibility of this method. Thin layers were deposited on glass and hemp fabric using dual pulsed laser (DPL) ablation on a compressed hemp seed target held in a stainless steel ring. The target was irradiated for 30 min with two synchronized pulsed laser beams, each with parameters of 30 mJ, 532 nm, pulse width of 10 ns, and a repetition rate of 10 Hz. Each beam had an angle of incidence with the target surface of 45°, and the angle between the two beams was also 45°. To improve laser absorption, two approaches were used: (1) HS-DPL/glass and HS-DPL/hemp fabric, in which a portion of the stainless steel ring was included in the irradiated area, and (2) HST-DPL/glass and HST-DPL/hemp fabric—hemp seeds were mixed with turmeric powder, which is known to improve laser interaction and biocompatibility. The FTIR and Micro-FTIR spectroscopy (ATR) performed on thin films compared to the target material confirmed the presence of hemp-derived phenolic compounds, including tetrahydrocannabinol (THC), cannabidiol (CBD), ferulic acid, and coumaric acid, along with other functional groups such as amides. The ATR spectra have been validated against Gaussian 6 numerical simulations. Scanning electron microscopy (SEM) and substance transfer tests revealed the microgranular structure of thin films. Through the analyzes carried out, the following were highlighted: spherical structures (0.3–2 μm) for HS-DPL/glass, HS-DPL/hemp fabric, HST-DPL/glass, and HST-DPL/hemp fabric; larger spherical structures (8–13 μm) for HS-DPL/glass and HST-DPL/glass; angular, amorphous-like structures (~3.5 μm) for HS-DPL/glass; and crystalline-like structures (0.6–1.3 μm) for HST-DPL/glass. Microparticle transfer from thin films on the hemp fabric to the filter paper at a human body temperature (37 °C) confirmed their suitability for TDD applications, aligning with the “whole plant medicine” or “entourage effect” concept. Granular, composite, thin films were successfully developed, capable of releasing microparticles upon contact with a surface whose temperature is 37 °C, specific to the human body. Each of the microparticles in the thin films obtained with the DPL technique contains phenolic compounds (cannabinoids and phenolic acids) comparable to those in hemp seeds, effectively acting as “microseeds.” The obtained films are viable for TDD applications, while the DPL technique ensures industrial scalability due to its low laser energy requirements. Full article

The accelerating threat of antimicrobial resistance (AMR) demands transformative strategies that go beyond conventional antibiotic therapies. Nanoparticles (NPs) have emerged as versatile antimicrobial agents, offering a combination of physical, chemical, and immunological mechanisms to combat multidrug-resistant (MDR) pathogens. Their small size, surface tunability, and ability to disrupt microbial membranes, generate reactive oxygen species (ROS), and deliver antibiotics directly to infection sites position them as powerful tools for infection control. This narrative review explores the major classes, mechanisms of action, and biomedical applications of antimicrobial NPs—including their roles in wound healing, implant coatings, targeted drug delivery, inhalation-based therapies, and the treatment of intracellular infections. We also highlight the current landscape of clinical trials and evolving regulatory frameworks that govern the translation of these technologies into clinical practice. A distinctive feature of this review is its focus on the interplay between NPs and the human microbiota—an emerging frontier with significant implications for therapeutic efficacy and safety. Addressing this bidirectional interaction is essential for developing microbiota-informed, safe-by-design nanomedicines. Despite promising advances, challenges such as scalability, regulatory standardization, and long-term biosafety remain. With interdisciplinary collaboration and continued innovation, antimicrobial NPs could reshape the future of infectious disease treatment and help curb the growing tide of AMR. Full article

Background/Objectives: Copper levels are significantly elevated in both the sera and tumor tissues of various cancers, including prostate cancer. It has therefore been suggested that targeting the elevated copper levels with copper chelators could lead to selective cancer treatment. Thus, several classes of low molecular weight copper-coordinating lipophilic compounds, as well as the newly developed copper complexes of appropriately functionalized polymers, are being investigated as promising novel anticancer therapeutics. Particularly, metal-containing polymers, or metallopolymers, are systematically investigated as anticancer agents or as drug delivery systems. This study aims to utilize the strong copper-chelating properties of hyperbranched polyethyleneimine (PEI) to develop PEI:Cu metallopolymers and evaluate their selectivity and anticancer properties against several prostate cancer cell lines. Methods: A series of PEI:Cu complexes at PEI/Cu ratios that ensure that no free copper ions are present in the solution are prepared and investigated against a human non-cancerous cell line and three prostate cancer cell lines of increasing metastatic potential. Results: PEI:Cu derivatives are cytotoxic against the human prostate carcinoma metastatic PC3 and DU145 cell lines, even at the lowest tested concentrations of 5 μg/mL, while against the non-cancerous HEK293 cells, all metallopolymer derivatives exhibit insignificant cytotoxicity up concentrations of 50 μg/mL. Their cytotoxic effect is associated with mitochondria membrane potential loss and ROS production increase. Conclusions: Hyperbranched polyethyleneimine–coordinated copper(II) metallopolymers, at low concentrations, selectively induce cytotoxicity in metastatic prostate cancer cell lines without compromising the viability of non-cancerous embryonic kidney cells. Full article

Today, cathinone and its synthetic derivatives are among the most popular narcotics in the world. Their different cytotoxic activities on humans are increasingly and rapidly being published in forensic reports and the scientific literature. New studies demonstrate that these compounds target the apoptosis of some human cancer cell lines. These results could potentially open a new perspective for cathinones’ use as potential therapeutic agents. Even so, the psychostimulant effects of these compounds require testing their activity in the form of drug delivery systems. In our work, we report on the first theoretical studies concerning the potential use of functionalised carbon nanotubes (CNTs) as carriers in the targeted transport of cathinones. Using density functional theory (DFT), we predicted cathinone–CNT interaction energies in environments with different polarity, as well as the stability of complexes in simplified models of healthy and cancer tissue. The results of the current work provide first-step insights into cathinone–CNT non-covalent complex formation in neutral and acidified environments. This study may serve as the theoretical basis for further experimental works on the possibility of using cathinone–CNT complexes in targeted anticancer therapy. Full article

Tumors are a major disease that seriously threatens human health, with their incidence and mortality rates increasing year by year. However, traditional therapies such as surgery, chemotherapy, and radiotherapy have significant limitations, including significant side effects and propensity for drug resistance. In recent years, with the rapid development of medical technology, RNA therapy has shown great potential as an emerging treatment method in anti-tumor therapy, bringing new hope for tumor treatment. RNA therapy mainly includes small interfering RNA, antisense oligonucleotides, and aptamers. Hydrogels, as a polymer material with three-dimensional network structure, have good biocompatibility and can effectively improve the efficiency of RNA delivery. This review specifically focuses on the application of hydrogels as RNA carriers in anti-tumor therapy, along with the classification, delivery advantages, and challenges. However, despite existing deficiencies in safety and targeting, hydrogel-mediated RNA delivery for tumor treatment still shows unique advantages and broad application prospects. In the future, research and cutting-edge innovations are expected to facilitate precision oncology solutions, offering superior treatment options and catalyzing the evolution of cancer management strategies. Full article

Multidrug resistance (MDR) remains a formidable barrier to successful cancer treatment, driven by mechanisms such as efflux pump overexpression, enhanced DNA repair, evasion of apoptosis and the protective characteristics of the tumour microenvironment. Nanoparticle-based delivery systems have emerged as promising platforms capable of addressing these challenges by enhancing intracellular drug accumulation, enabling targeted delivery and facilitating stimuli-responsive and controlled release. This review provides a comprehensive overview of the molecular and cellular mechanisms underlying MDR and critically examines recent advances in nanoparticle strategies developed to overcome it. Various nanoparticle designs are analysed in terms of their structural and functional features, including surface modifications, active targeting ligands and responsiveness to tumour-specific cues. Particular emphasis is placed on the co-delivery of chemotherapeutic agents with gene regulators, such as siRNA, and the use of nanoparticles to deliver CRISPR/Cas9 gene editing tools as a means of re-sensitising resistant cancer cells. While significant progress has been made in preclinical settings, challenges such as tumour heterogeneity, limited clinical translation and immune clearance remain. Future directions include the integration of precision nanomedicine, scalable manufacturing and non-viral genome editing platforms. Collectively, nanoparticle-based drug delivery systems offer a multifaceted approach to combat MDR and hold great promise for improving therapeutic outcomes in resistant cancers. Full article

The increasing global health crisis of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, and Huntington’s disease is worsening because of a rapidly increasing aging population. Disease-modifying therapies continue to face development challenges due to the blood–brain barrier (BBB), which prevents more than 98% of small molecules and all biologics from entering the central nervous system. The therapeutic landscape for neurodegenerative diseases has recently undergone transformation through advances in targeted drug delivery that include ligand-decorated nanoparticles, bispecific antibody shuttles, focused ultrasound-mediated BBB modulation, intranasal exosomes, and mRNA lipid nanoparticles. This review provides an analysis of the molecular pathways that cause major neurodegenerative diseases, discusses the physiological and physicochemical barriers to drug delivery to the brain, and reviews the most recent drug targeting strategies including receptor-mediated transcytosis, cell-based “Trojan horse” approaches, gene-editing vectors, and spatiotemporally controlled physical methods. The review also critically evaluates the limitations such as immunogenicity, scalability, and clinical translation challenges, proposing potential solutions to enhance therapeutic efficacy. The recent clinical trials are assessed in detail, and current and future trends are discussed, including artificial intelligence (AI)-based carrier engineering, combination therapy, and precision neuro-nanomedicine. The successful translation of these innovations into effective treatments for patients with neurodegenerative diseases will require essential interdisciplinary collaboration between neuroscientists, pharmaceutics experts, clinicians, and regulators. Full article

Wound healing is a physiological process including haemostasis, inflammation, proliferation, and remodelling. Acute wounds typically follow a predictable healing process, whereas chronic wounds cause prolonged inflammation and infection, failing to progress through typical healing phases and presenting significant clinical challenges. A combination of wound care techniques and therapeutic agents is required to manage chronic wounds effectively. Curcumin is a bioactive compound derived from Curcuma longa and has gained attention for its potent antioxidant, anti-inflammatory, and antibacterial properties. The first part of this review aims to provide a comprehensive overview of the physiology of wound healing, focusing on the pathophysiology and management of acute and chronic wounds, followed by the biological activity of curcumin in wound healing, emphasising its impact on promoting tissue repair. Finally, this review explores curcumin-loaded dressings, such as hydrogels, nanofibrous membranes, polymeric micelles, and films, offering controlled drug release and targeted curcumin delivery to enhance wound healing. Full article

Proteolysis-targeting chimeras (PROTACs) selectively degrade target proteins by recruiting intracellular E3 ubiquitin ligases, overcoming the limitations of traditional small-molecule inhibitors that merely block protein function. This approach has garnered significant interest in precision cancer therapy. However, the clinical translation of PROTACs is hindered by their typically high molecular weight, poor membrane permeability, and suboptimal pharmacokinetic properties. Nanodrug delivery technologies represent a promising approach to overcome the limitations of PROTACs. By encapsulating, conjugating, or integrating PROTACs into functionalized nanocarriers, these systems can substantially enhance solubility and biostability, enable tumor-targeted and stimuli-responsive delivery, and thereby effectively alleviate the “hook effect” and minimize off-target toxicity. This review systematically outlines the primary design strategies for current nano-PROTAC delivery systems, including physical encapsulation, chemical conjugation, carrier-free self-assembly systems, and intelligent “split-and-mix” delivery platforms. We provide an overview and evaluation of recent advances in diverse nanomaterial carriers—such as lipid-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, biological carriers, and hybrid nanoparticles—highlighting their synergistic therapeutic potential for PROTACs delivery. The clinical translation prospects of these innovative systems are also discussed. This comprehensive analysis aims to deepen the understanding of this rapidly evolving field, address current challenges and opportunities, promote the advancement of nano-PROTACs, and offer insights into their future development. Full article

Background/Objectives: Liver cancer is considered one of the most dangerous types of cancer due to both the patients’ and the physician’s delay in diagnosis. Metal/ligand complexes represent antitumor drugs; however, they have several limitations such as a lack of specificity that results in damage to healthy organs. Therefore, there is a need for a material that improves specificity and decreases side effects. Magnetite nanoparticles (MNPs) show outstanding findings in the targeting and treatment of cancer-diseased organs. Methods: Herein, a metal/ligand palladium complex with antitumor activity was prepared and loaded onto magnetite nanoparticles for the treatment of liver cancer. The proposed structures with the lowest energy geometries were identified by density functional theory (DFT) utilizing the Gaussian09 program. Molecular docking simulation was conducted on an HP Pavilion dv6 Notebook PC equipped with an AMD Phenom™ N930 Quad processor. Afterward, the prepared nano-systems were investigated using FTIR and TEM. In vitro drug release measurement was evaluated in PBS at different time intervals. Eventually, the selectivity of these nano-systems was investigated using an animal rat model. Results: The results showed that MNPs with a crystalline structure and superparamagnetic characteristics (Ms = 71.273 emu/g) were created with a large surface area (63.75 m²/g), and they were validated to be acceptable for drug delivery applications. The palladium complex [Pd(DMEN)Cl₂] loaded onto magnetite released highly in acidic circumstances (pH 4.5), implying that it could be employed for targeted therapy of liver cancer. Conclusions: In vivo investigations in a rat model of liver cancer induced by diethylnitrosamine and thioacetamide (DEN/TAA) showed that the combination of the palladium complex and magnetite demonstrated a potent anticancer therapeutic activity on liver cancer in rats, improving liver function and structure while mitigating inflammation. Full article

Icariin (ICA) is a bioactive flavonoid compound extracted from Epimedium plants. In recent years, it has attracted significant research interest in the field of bone tissue repair due to its pharmacological effects via multiple targets and pathways. Studies have shown that ICA promotes the osteogenic differentiation of mesenchymal stem cells (MSCs) and enhances bone matrix formation by regulating signaling pathways such as Akt and Wnt/β-catenin. It concurrently inhibits osteoclast activity to maintain the balance of bone remodeling, thereby simultaneously stimulating new bone regeneration and suppressing bone resorption. At the same time, ICA exerts potent anti-inflammatory and antioxidant effects and promotes angiogenesis, improving the local microenvironment of bone injury and significantly facilitating the regeneration of bone and cartilage tissues. Additionally, ICA exhibits notable protective effects in multiple organ systems including the cardiovascular, hepatic, renal, and nervous systems. Specifically, ICA reduces cardiomyocyte apoptosis and fibrosis to preserve cardiac function, improves hepatic metabolic function and alleviates oxidative stress, attenuates renal inflammation and fibrosis, and—through neuroprotective actions—reduces neuroinflammation and promotes neuronal survival. These multi-organ effects help optimize the systemic environment for bone healing. However, ICA faces significant pharmacokinetic challenges. It has low oral bioavailability (due to poor absorption and extensive first-pass metabolism) as well as a short half-life. Consequently, maintaining effective drug concentrations in vivo is difficult, which limits its therapeutic efficacy and impedes clinical translation. To fully realize its regenerative potential, advanced drug delivery strategies (e.g., nanocarrier-based delivery systems) are being explored to enhance ICA’s bioavailability and prolong its duration of action. Overall, ICA’s multi-modal actions on bone cells, the immune microenvironment, and systemic factors make it a promising multi-target agent for bone regeneration. Addressing its pharmacokinetic limitations through optimized delivery and conducting further clinical studies will be crucial to realize its full therapeutic potential. This review provides a comprehensive overview of recent advances and challenges in translating ICA’s benefits into orthopedic therapy. Full article

Microtubules play a key role in cell division and cell migration. Thus, microtubule-targeting agents (MTAs) are pivotal in cancer therapy due to their ability to disrupt cell division microtubule dynamics. Traditionally divided into stabilizers and destabilizers, MTAs are increasingly being repurposed for central nervous system (CNS) applications, including brain malignancies such as gliomas and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Microtubule-stabilizing agents, such as taxanes and epothilones, promote microtubule assembly and have shown efficacy in both tumour suppression and neuronal repair, though their CNS use is hindered by blood–brain barrier (BBB) permeability and neurotoxicity. Destabilizing agents, including colchicine-site and vinca domain binders, offer potent anticancer effects but pose greater risks for neuronal toxicity. This review highlights the mapping of nine distinct tubulin binding pockets—including classical (taxane, vinca, colchicine) and emerging (tumabulin, pironetin) sites—that offer new pharmacological entry points. We summarize the recent advances in structural biology and drug design, enabling MTAs to move beyond anti-mitotic roles, unlocking applications in both cancer and neurodegeneration for next-generation MTAs with enhanced specificity and BBB penetration. We further discuss the therapeutic potential of combination strategies, including MTAs with radiation, histone deacetylase (HDAC) inhibitors, or antibody–drug conjugates, that show synergistic effects in glioblastoma models. Furthermore, innovative delivery systems like nanoparticles and liposomes are enhancing CNS drug delivery. Overall, MTAs continue to evolve as multifunctional tools with expanding applications across oncology and neurology, with future therapies focusing on optimizing efficacy, reducing toxicity, and overcoming therapeutic resistance in brain-related diseases. Full article

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article