Search Results (1,611)

Background/Objectives: This study developed a targeted drug delivery nanoplatform for treating HER2-positive breast cancer. The nanoplatform encapsulated two hydrophobic anticancer agents, neratinib (NTB) and docetaxel (DTX), within nanoparticles (DTX+NTB−NP) functionalized for conjugation to trastuzumab to form trastuzumab-tagged nanoparticles (TRZ−NP). Trastuzumab is a HER2-specific monoclo-nal antibody that binds to HER2 receptors, blocking signal transduction and inducing an-tibody-dependent cellular cytotoxicity (ADCC). Upon receptor-mediated endocytosis, neratinib inhibits cytosolic HER2 signaling, while docetaxel disrupts mitotic cell division, collectively leading to tumor cell death. Methods: Nanoparticles were fabricated by the nanoprecipitation technique, followed by surface modification with a crosslinker and a targeting moiety. DTX+NTB−NP, TRZ−NP, and singly loaded nanoparticles (NTB−NP and DTX−NP) were characterized and their effects evaluated in HER2-positive cancer cell line and xenograft model. Results: In vitro antiproliferation assay in SKBR-3 cell line re-veals a dose and time-dependent cytotoxicity. There was no significant difference in cyto-toxicity observed between DTX+NTB−NP and its free form (DTX+NTB) [p = 0.9172], and between TRZ−NP and its free form (TRZ+DTX+NTB) [p = 0.6750]. However, TRZ−NP, at half the concentration of the singly loaded nanoparticles, significantly reduced the viabil-ity of SKBR-3 cells compared to pure trastuzumab (TRZ) [p < 0.001], NTB−NP [p = 0.0019], and DTX−NP [p = 0.0002]. In vivo evaluation in female athymic nude mice showed sig-nificant log relative tumor volume (%) reduction in groups treated with TRZ−NP and DTX+NTB−NP compared to PBS (phosphate-buffered saline) controls (p ≤ 0.001 and p ≤ 0.001), respectively. Notably, TRZ−NP demonstrated a statistically significant regression in the log relative tumor volume (%) compared to DTX+NTB−NP (p = 0.001). Conclusions: These findings underscore the therapeutic potential and suitability of these nanoplatforms for the precise and controlled targeting of HER2-positive tumors. This study is the first to synchronize the delivery of multiple agents-docetaxel, neratinib, and trastuzumab-within a nanoparticle system for treating HER2-positive tumors, offering a promising strategy to enhance treatment outcomes for HER2 positive breast cancer patients. Full article

Background/Objectives: Natural products exhibit significant immunomodulatory potential but face severe efficacy loss in three-dimensional (3D) tumor models. This review comprehensively examines the penetration–activity trade-off and proposes integrated strategies for developing effective natural product-based cancer immunotherapies. Methods: We analyzed formulation strategies across three natural product categories (hydrophobic, macromolecular, stability-sensitive), evaluating penetration enhancement versus activity preservation in spheroids, organoids, and advanced 3D platforms. Results: Tumor spheroids present formidable barriers: dense extracellular matrix (33-fold increased fibronectin), pH gradients (7.4 → 6.5), and extreme cell density (6 × 10⁷ cells/cm³). While nanoparticles, liposomes, and cyclodextrins achieve 3–20-fold penetration improvements, biological activity frequently declines through conformational changes, incomplete release (10–75%), and surface modification interference. Critically, immune cells remain peripheral (30–50 μm), questioning deep penetration pursuit. Patient-derived organoids display 68% predictive accuracy, while emerging vascularized models unveil additional complexity. Food and Drug Administration (FDA) Modernization Act 2.0 enables regulatory acceptance of these advanced models. Conclusions: Effective therapeutic outcomes depend on maintaining immunomodulatory activity in peripherally-located immune cell populations rather than achieving maximum tissue penetration depth. Our five-stage evaluation framework and standardization protocols guide development. Future priorities include artificial intelligence-driven optimization, personalized formulation strategies, and integration of multi-organ platforms to bridge the critical gap between enhanced delivery and therapeutic efficacy. Full article

Functional hydrogels are a growing class of soft materials. Functional hydrogels are characterized by their three-dimensional (3D) polymeric network and high water-retention capacity. Functional hydrogels are deliberately engineered with specific chemical groups, stimuli-responsive motifs, or crosslinking strategies that impart targeted biomedical or environmental roles (e.g., drug delivery, pollutant removal). Their capacity to imitate the extracellular matrix, and their biocompatibility and customizable physicochemical properties make them highly suitable for biomedical and environmental applications. In contrast, non-functional hydrogels are defined as passive polymer networks that primarily serve as water-swollen matrices without such application-oriented modifications. Recent progress includes stimuli-responsive hydrogel designs. Stimuli such as pH, temperature, enzymes, light, etc., enable controlled drug delivery and targeted therapy. Moreover, hydrogels have shown great potential in tissue engineering and regenerative medicine. The flexibility and biofunctionality of hydrogels improve cell adhesion and tissue integration. Functional hydrogels are being explored for water purification by heavy metal ion removal and pollutant detection. The surface functionalities of hydrogels have shown selective binding and adsorption, along with porous structures that make them effective for environmental remediation. However, hydrogels have long been postulated as potential candidates to be used in clinical advancements. The first reported clinical trial was in the 1980s; however, their exploration in the last two decades has still struggled to achieve positive results. In this review, we discuss the rational hydrogel designs, synthesis techniques, application-specific performance, and the hydrogel-based materials being used in ongoing clinical trials (FDA–approved) and their mechanism of action. We also elaborate on the key challenges remaining, such as biocompatibility, mechanical stability, scalability, and future directions, to unlocking their multifunctionality and responsiveness. Full article

Cellulose nanocrystals (CNCs), derived from renewable cellulose sources, have emerged as a versatile class of nanomaterial with exceptional mechanical strength, tuneable surface chemistry and inherent biocompatibility. In the scenario of contemporary commercial hydrogel products, which are expensive and rely on synthetic materials, the sustainable origin and unique physicochemical properties have positioned CNCs as promising sustainable functional building blocks for next-generation hydrogels in biomedical applications. Over the past decade, CNC-based hydrogels have gained momentum as soft biomaterials capable of interacting with diverse tissue types, predominantly demonstrated through in vitro cell line studies. This review critically examines the current landscape of research on biomedical applications of CNC-based hydrogels, focusing on their biomedical utility across 22 systematically screened studies. It revealed applications spanning around bone and cartilage tissue engineering, wound healing, medical implants and sensors, and drug delivery. We highlight the predominance of microcrystalline cellulose as the CNC source and sulfuric acid hydrolysis as the preferred extraction method, with several studies incorporating surface modifications to enhance functionality. Despite growing interest, there remains a lack of data for transitioning towards human clinical studies and commercialisation. Hence, this review highlights the pressing need for scalable, sustainable, and affordable CNC-based hydrogel systems that can democratise access to advanced biomedical technologies. Full article

Breast cancer has now surpassed lung cancer as the leading cause of cancer-related deaths among women worldwide. Given the urgent need for more effective treatment, extracellular vesicles (EVs) have gained attention as versatile and promising drug delivery systems. Derived from a variety of cell types, EVs can be loaded with therapeutic cargo or engineered to present specific surface ligands and receptors. These EV modifications enable them to overcome many limitations associated with conventional therapies. In this review, we highlight current methodologies for loading small molecule drugs, RNA-based therapeutics, and proteins into EVs through both pre-isolation (endogenous) and post-isolation (exogenous) methods. We further discuss recent advances in EV surface engineering strategies aimed at improving tumor-specific targeting and immunotherapeutic efficacy in breast cancer. Full article

Breast cancer (BC) is a major cause of cancer-related mortality. Mortalin and Vimentin—two proteins implicated in BC progression and metastasis—have been identified as binding partners of the Secretion Modification Region (SMR) peptide from the HIV Nef protein. These interactions disrupt exosome release and offer novel therapeutic strategies. This study investigates the binding interactions between the SMR peptide, Mortalin, and Vimentin using surface plasmon resonance (SPR), co-immunoprecipitation (Co-IP), and Western blot assays. We also map the SMR binding sites on Mortalin through scanning peptide mapping and then identify a similar site on the Vimentin protein. Based on these data, we propose that the SMR peptide and its analogs interact with specific amino acid sequences in Mortalin and Vimentin, thereby disrupting cellular processes essential for Epithelial–Mesenchymal Transition (EMT) and tumor progression. SPR analysis revealed that the Nef protein exhibited the highest binding affinity to Vimentin (KD = 0.75 ± 1.1 nM) and Mortalin (KD = 3.16 ± 0.03 nM). The SMRwt peptide also demonstrated direct binding to both proteins with micromolar affinities (KD = 6.63 ± 0.74 µM for Vimentin; KD = 20.73 ± 2.33 µM for Mortalin), though the binding affinity was weaker than the full Nef protein. Co-IP experiments using MDA-MB-231, MCF-7, and BT474 BC cell lines confirmed that SMRwt, but not SMRmut, co-immunoprecipitated with Mortalin. Western blot analysis validated these interactions. Further, Mortalin peptide #56, derived from the substrate-binding domain, did not bind the SMR domain or inhibit Nef function. In contrast, peptides #61 and #62 from the C-terminal domain of Mortalin bound the SMR domain and effectively inhibited Nef activity. Notably, Mortalin peptide #61 inhibited SMRwt binding to both Mortalin and Vimentin, disrupting complex formation on the SPR sensor chip. These findings suggest that specific Mortalin-derived peptides can block SMR interactions, offering a potential therapeutic mechanism. Full article

This work aimed to synthesize rigid polyurethane foams with improved functional properties through modification with the addition of cellulose in the form of straw: unmodified, silanized, and silanized with the addition of fumed silica. The prepared rigid polyurethane foams contained 0.5; 1; and 3 parts by weight of the modifier about the weight of the polyol used. As part of the work, a number of tests were carried out to determine the impact of the modifiers used on the reaction kinetics and on the functional properties of rigid polyurethane foams. Silanization improved thermal stability and interfacial compatibility, while silica further enhanced porosity and surface activity. The optimal properties were obtained at low loadings: 0.5 wt.% provided the best mechanical strength, and 1 wt.% yielded the most uniform cell morphology and density. Higher contents increased porosity, reduced strength, and lowered water resistance. Dynamic mechanical analysis confirmed predominantly elastic behavior, with silica-modified fillers offering the most stable thermomechanical response. Overall, even small amounts of modified straw enhanced mechanical, structural, and water-resistant properties, demonstrating its potential as a sustainable and cost-effective biofiller for eco-friendly polyurethane foams. Full article

Idiopathic pulmonary fibrosis (IPF) is currently defined as a progressive fibrosing interstitial lung disease (ILD) associated with a histopathologic and radiologic pattern of usual interstitial pneumonia (UIP). The relationship between IPF and particles is described, and a pathogenesis for the disease is proposed based on an association with these exposures. In clinical studies and epidemiological investigations, the majority of IPF diagnoses are associated with particle exposures. Cigarette smoking presents the greatest particle challenge in any society, and a relationship with IPF has repeatedly been demonstrated. Environmental exposures to particles other than cigarette smoking, including biomass fuel smoke and ambient air pollution, as well as numerous occupational particle exposures, have also been associated with IPF. The pathogenesis of the disease includes a complexation and sequestration of cell iron at the particle surface, which results in a functional cell deficiency of the requisite metal. In response to the insufficiency of metal in cells, there is the synthesis of biopolymers, including exopolysaccharides (e.g., hyaluronic acid), which accumulate in the extracellular matrix. These biopolymers complex iron and, following depolymerization, facilitate the delivery of the metal intracellularly via receptor-mediated uptake. This process reverses the functional iron deficiency introduced by the particle. Pulmonary fibrosis after particle exposure reflects a response to the modification of a functional intracellular iron deficiency in the lower respiratory tract. The temporal and spatial heterogeneity of IPF results from a dose–response with retained particles and reversibility of the fibrosis. Full article

Immune cells play a pivotal role in orchestrating tissue repair, executing functions such as debris clearance, extracellular matrix remodeling, and modulation of cytokine secretion profiles. However, when their activity is dysregulated or inadequately directed, these same processes can give rise to chronic inflammation and foreign body reactions (FBR), ultimately leading to fibrosis and compromised biomaterial performance. The immunological landscape following injury or biomaterial implantation is profoundly influenced by the physicochemical properties of material surfaces. By strategically tailoring these surface characteristics, it becomes possible to modulate immune cell responses—governing their adhesion, recruitment, proliferation, polarization, and cytokine expression patterns. This review elucidates the multifaceted roles of immune cells in tissue repair and their dynamic interactions with implanted biomaterials. It then explores how specific surface attributes—such as topography, chemistry, stiffness, and wettability—influence immune behavior. Particular emphasis is placed on recent advances in surface modification techniques aimed at engineering next-generation biomaterials that mitigate adverse immune responses while actively promoting regenerative healing. The review concludes by offering critical insights into the future of immunomodulatory biomaterial design, highlighting both emerging opportunities and persisting challenges in the field. Full article

Directed cell migration is crucial for numerous biological processes, including tissue regeneration and cancer metastasis. However, conventional symmetrical micropatterns typically result in bidirectional cell migration guidance instead of unidirectional guidance. In this study, polydimethylsiloxane (PDMS)-based platforms with asymmetrical arrowhead micropatterns, nanopillars, and selective fibronectin coating were developed to enhance unidirectional cell migration. The platforms were fabricated using nanoimprint lithography and PDMS replication techniques, allowing for precise control over surface topography and biochemical modification. The MC3T3 osteoblastic cells cultured on these platforms demonstrated significantly enhanced directional migration, characterized by increased displacement, and directional alignment with micropattern orientation compared to symmetrical patterns. Quantitative analyses revealed that asymmetrical arrowheads combined with nanopillars induced more focal adhesions and F-actin polarization at cell front regions, supporting the observed unidirectional cell migration enhancement. These results confirm that integrating micropattern asymmetry, nanoscale features, and biochemical functionalization synergistically promotes unidirectional cell migration. The developed platforms offer valuable insights and practical strategies for designing advanced biomaterials capable of precise spatial cell guidance that can be applied to the designs of organ-on-a-chip systems. Full article

Methicillin-resistant S. aureus is a problematic pathogen due to its high-risk infections and resistance mechanisms. To fight against this bacterium, novel antimicrobial sources and new delivery systems must be developed. Antimicrobial polyurethanes for developing biomaterials can function as preventive strategies. In this study, we explore the synthesis of partially renewable polyurethanes as biomaterial carriers of novel antimicrobials. An antibacterial extract from a Streptomyces sp. strain and its inclusion complexes with β-cyclodextrin, used as an additional protective approach, were incorporated into castor oil-based polyurethane films through bulk or surface loading. The inclusion complexes were characterized to confirm host–guest interactions. The films were characterized by FTIR, XRD spectra, surface SEM images, hydrophilicity, thermal stability, and mechanical performance. FTIR suggested successful polyurethane synthesis. The polymers were semicrystalline and thermally stable until 260 °C, and Tg ranged between −16.9 and −9 °C. Bulk modification decreased the mechanical performance of the films. Surface modification promoted good antibacterial performance but cytotoxic potential against HDFa cells. However, PU active films showed favorable properties and hemocompatibility, making them a promising alternative for applications such as short-term dressings, serving as an antimicrobial delivery system and a preventive strategy against methicillin-resistant S. aureus. Full article

Nanoporous gold nanoparticles (np-AuNPs) combine inertness, a nanoscale structure, and a porous framework with high surface area, conductivity, and biocompatibility, making them ideal for biosensing, catalysis, fuel cells, and drug delivery. Their open pore structure and low-coordinated atoms enhance biomolecule capture and mass transfer, while their tunable size, pore volume, and ease of surface modification make them promising biosensor transducers. However, synthesizing colloidal np-AuNPs in a simple way with controllable size and scalability remains challenging. The existing approaches mostly rely on specialized equipment, complex setups, and expert knowledge, while still facing challenges in terms of scalability. In this study, we present a simple, seedless, wet-chemical synthesis of colloidal np-AuNPs via the co-reduction of Au/Ag alloys followed by dealloying. By adjusting the Au:Ag ratio, we produced np-AuNPs sized ~120–530 nm, which were immobilized on electrodes for detecting lipopolysaccharide (LPS), a toxic component of Gram-negative bacterial membranes. The LPS biosensor exhibited excellent sensitivity towards detecting wild-type LPS, with a low limit of detection (LOD) of 0.1244 ng/L. This work demonstrates the effective synthesis and application of np-AuNPs in LPS biosensing. Full article

To investigate granulocytes under laboratory conditions, centrifugation steps are typically required for the isolation of neutrophil granulocytes from whole blood. However, only a few studies to date have addressed the direct effects of centrifugation itself on the functional state of neutrophils. This study aims to elucidate the mechanisms that contribute to the modification of granulocytes during centrifugation. We hypothesize that granules sustain morphological alterations during centrifugation, leading to the release of highly potent antimicrobial enzymes into the cytosol of the cells. Neutrophils were isolated from whole blood using different methods with and without centrifugation and analyzed by flow cytometry, ELISA, and mass spectrometry. Our findings demonstrate that intracellular granules incur damage during centrifugation, resulting in the presence of intragranular enzymes within the cytosol. Furthermore, the formation of the highly reactive hypochlorous acid (HOCl) as a consequence of centrifugation could be verified. The generation of intracellular HOCl may explain many of the alterations observed in neutrophils following centrifugation-based isolation, including modified surface antigen expression and altered responses to stimulation. In future studies, centrifugation steps during cell isolation should be avoided. The more time-consuming but gentler method of sedimentation is preferable and can be used as long as it is not necessary to obtain a highly purified neutrophil fraction. Full article

For tetragonal lead tungstate (PWO) and other tetragonal crystals, we study modifications of the Bertin surfaces induced by either the distortion of crystallographic cells, the applied plane stress, or cell misalignment with respect to the specimen faces. In both cases, the distortions of the Bertin surfaces result in the reshaping of the interference pattern observed by conoscopy. We provide, for different observation directions of the crystals, analytical relations that allow for the evaluation of the optic plane and the optical indicatrix rotation with or without stress. By the means of these relations, interference image reshaping allows us to detect, provided that some conditions hold, the crystallographic axes’ rotation. This work is a theoretical study aiming to evaluate the optic axes and crystallographic cell orientation by means of conoscopic observations. Full article

The aim of this study was to evaluate the haemostatic potential and biocompatibility of a newly developed composite material for its use in blood-contacting applications. Based on promising reports on polylactide (PLA), sodium alginate (ALG), and bioactive additives such as hardystonite (HT) and zinc sulphide (ZnS), a melt-blown PLA nonwoven was modified via dip-coating using an ALG solution as a matrix for incorporating HT and ZnS particles, resulting in the PLA-ALG-ZnS-HT composite. The material was characterised in terms of surface morphology, specific surface area, pore volume, average pore size, and zeta potential (pH~7.4). Haemostatic activity was assessed by measuring blood coagulation parameters, while biocompatibility was evaluated through the viability of human peripheral blood mononuclear (PBM) cells and human foreskin fibroblasts (Hs68). Genotoxicity was analysed using the comet assay and plasmid relaxation test. Results confirmed a uniform alginate coating with dispersed HT and ZnS particles on PLA fibres. The modification increased the surface area and pore volume and caused a shift toward less negative zeta potential. Haemostatic testing showed prolonged activated partial thromboplastin time (aPTT), likely due to Zn²⁺ interactions with clotting factors. Biocompatibility tests showed high cell viability and no genotoxic effects. Our findings suggest that the PLA-ALG-ZnS-HT composite is safe for blood and skin cells and may serve as an anticoagulant material. Full article