Breast cancer is one of the main causes of cancer-related death worldwide in women. Conventional treatment of breast cancer, including surgery and chemotherapy, face challenges such as tumor resistance, damaged organs due to the cytotoxicity of anticancer drugs, and poor drug circulation. Recently, several drug delivery vehicles have been developed for targeted breast cancer therapy enhancing drug bioavailability, solubility, and penetration while minimizing side effects and toxicity. In addition to chemotherapeutic drugs, antioxidants derived from plants have gained attention as promising agents for the treatment of breast cancer. This review explores the effect of natural product antioxidants on breast cancer and summarizes state-of-the-art studies utilizing various drug delivery systems to enhance the delivery of antioxidants to breast cancer.

To survive, cells are able to adapt to a wide range of adverse conditions, such as varying pH from optimal (~7.4). They do this through mechanisms including acid-sensing ion channels, which alter cytosolic ion content and thus the cell’s electrophysiological profile. However, the impact of this adaptation on cellular electrophysiology remains unexplored. We investigated the effects of culture at a range of extracellular pH on the electrophysiological features of breast cancer cell lines MDA-MB-231 and MCF-7. Cells were subject to an acid–neutral–base pH from 3.0 to 9.2, after which their membrane potential (Vm), cytoplasm conductivity σcyto, effective membrane conductance Geff, and ζ-potential were measured. Cells were also analyzed after permeabilization, to examine whether observed changes were due to cell surface chemistry, or to Vm. Both cell lines exhibited different electrophysiological phenotypes in acidic environments (pH < 6.7); MDA-MB-231 exhibited statistically significant differences in ζ-potential, Vm, Geff and σcyto; MCF-7 only exhibited significant differences in σcyto. These findings suggest cells adapt to acidic microenvironments by altering Vm and potentially ζ-potential, reducing the extracellular potential, and hence potentially lowering proton concentration at the extracellular membrane surface. This offers new insights into potential therapeutic avenues to target the pH-dependent adaptations of cancer cells.

Breast cancer is the most common type of cancer in women worldwide, and elevated levels of reactive oxygen species (ROS) are one of hallmarks in breast cancer. Immunotherapy is one of cancer therapy, which can help the immune system fight cancer. In order to treat breast cancer efficiently, it is critical to understand the interactions between tumor cells, immune cells, and their microenvironment such as higher level of ROS. Here, we explores the impact of ROS on MDA-MB-231 cells - a triple-negative breast cancer cell line, and THP-1 cells - a human leukemia monocytic cell line, and THP-1 derived macrophages.This study demonstrated that THP-1 monocytes were more sensitive to exogenous H2O2, and 100 μM or higher H2O2 concentrations induced cytotoxicity via oxidative stress. MDA-MB-231 cells had higher levels of intracellular ROS than other types of cells; however, they are more resistant to exogenous H2O2 than THP-1 cells. THP-1 derived macrophages (M0 and M1) were found to have a good ability to fight MDA-MB-231 cancer cells. M0 or M1 increased the dead cell population of MDA-MB-231 cells when they were co-cultured with MDA-MB-231 cells. The results explain why monocytes differentiates into macrophages to response inflammatory process in vivo.

Biofilm associated urinary tract infections (UTIs) are not routinely distinguished from planktonic infections in clinical diagnostics, despite their distinct physiological behavior and clinical outcomes. Here, we present an impedance based bioelectronic approach that enables functional differentiation of biofilm infection using frequency resolved electrochemical impedance spectroscopy (EIS) on PEDOT:PSS-coated gold electrodes. To establish these impedance signatures, electroactive (Pseudomonas aeruginosa) and non-electroactive (Escherichia coli) biofilms were used as model systems. Distinct electrical fingerprints were identified across frequency domains, including a pronounced low frequency impedance decrease (ΔZ at 1 Hz ≈ −1000 Ω) associated with redox mediated electron transfer in electroactive biofilms, and a significant increase in charge transfer resistance (Rct ≈ 80 Ω) characteristic of insulating, EPS-rich non-electroactive biofilms, while negligible charge transfer resistance was observed in the absence of biofilm. Building on this framework, the impedance fingerprints were applied to clinical urine samples, enabling differentiation between biofilm and non biofilm associated UTIs, and healthy controls. Notably, most biofilm-associated UTI samples exhibited impedance signatures consistent with non-electroactive E. coli, the predominant uropathogen in UTI. Finally, introducing the urine samples into a PEDOT: PSS embedded biofilm-on-chip platform enabled continuous monitoring of biofilm formation from UTI samples and their response to antibiotic treatment, highlighting the ability to detect biofilm persistence and tolerance in clinical case under physiologically relevant environment. This work establishes impedance fingerprinting as a robust and translational strategy for the detection, classification, and functional assessment of biofilm associated UTIs, with strong potential for personalized antibiotic screening and clinical decision support.

Triple-negative breast cancer (TNBC) remains one of the most aggressive breast cancer subtypes, with limited targeted treatment options. This study investigates the efficacy of folic acid (FOL) as a targeting molecule for TNBC. It also examines whether the cellular uptake of FOL is influenced by acidic pH, a major feature of tumor tissue. A multifunctional FITC-Catalase-Folate (FITC-CAT-FOL) conjugate was developed and optimized to combine fluorescence tracking, enzymatic activity, and receptor targeting. Two conjugation strategies were compared to evaluate how reaction order affects labeling efficiency and catalase (CAT) stability. The optimized FITC-CAT-FOL configuration showed higher fluorescence, efficient FOL incorporation, and greater retention of catalytic activity compared to the reverse order (FOL-CAT-FITC). The conjugate maintained stable enzymatic function across different pH levels and demonstrated enhanced cellular uptake and viability at mildly acidic to neutral conditions (pH 6-7.4) through folate receptor-mediated endocytosis in TNBC cells. Fluorescence microscopy further confirmed enhanced intracellular localization of the conjugate under mildly acidic to neutral conditions. Moreover, cells treated with FITC-CAT-FOL showed higher viability and improved tolerance to oxidative stress, supporting the conjugate's biocompatibility and protective antioxidant function. These results confirm that folic acid exhibits strong affinity toward TNBC cells under physiological and tumor-relevant pH, supporting its use as an effective targeting molecule in enzyme-based drug delivery systems.

Breast cancer is the most prevalent cancer among women worldwide. Unlike normal cells, breast cancer cells exhibit a reversed pH gradient characterized by a lower extracellular pH (pHe, ∼6.7-7.1) and a higher intracellular pH (pHi, ∼7.4). Modulation of extracellular pH can influence the growth and viability of these cells. In this study, we examined the effects of ten organic acids on MDA-MB-231 metastatic breast cancer cells. Among ten organic acids, dicarboxylic acids (succinic acid (SA), fumaric acid (FA), and tartaric acid (TA)) and tricarboxylic acid (citric acid (CA)) exhibited significantly higher cytotoxicity compared to the others including monocarboxylic acid. Further analysis revealed that their cytotoxic effects were primarily induced by acidic pH associated with the number of COOH in their chemical structures. These acids also impacted cell viability, density, and morphology in both 2D cultures and 3D spheroid models. The results of this research can aid in the development of innovative anticancer drugs treating breast cancer.

Multi-material 3D printing enables the production of objects with different materials deposited selectively at suitable locations. Multi-material 3D printing can be used to produce advanced contact lenses with novel functionalities. However, further advancements are still required to make it commercially feasible. Here, multi-material 3D printing is explored with vat photopolymerization printer to produce contact lenses for color vision correction. Fluorescent dyes Atto565, Atto425, Atto465, and Atto495 are added to the 3D-printed contact lenses for selective wavelength filtering. Multiple dyes can be added to different layers using a multi-material 3D printing process. The contact lenses were printed using hydroxyethyl methacrylate (HEMA) and polyethylene glycol diacrylate (PEGDA) hydrogel. A HEMA:PEGDA concentration of 35:1 was utilized to provide optimal material properties for 3D-printed contact lenses. Extensive characterization studies were performed on these contact lenses, including water absorption, contact angle, cytotoxicity, hydrogel degradation, dye stability, and tensile behavior. Color vision perception modeling simulation and patient trials were performed to evaluate the performance of multi-material filters. The 3D-printed lenses displayed good optical quality and relatively good materials properties. The results indicate that, with further improvements, 3D printed multi-material contact lenses hold significant potential for color vision correction and various ocular applications.

Transdermal microneedles (MNs) have emerged as a powerful new technique for medicine and drug delivery. MNs are highly bioavailable, biocompatible, and non-invasive drug delivery systems. Catalase is one of the antioxidant enzymes that decomposes hydrogen peroxide to overcome oxidative damage. Enzymatic proteins such as catalase have a great therapeutic potential; however, their application in vivo is limited until now. For example, when they are administered orally, therapeutic proteins are easily degraded by proteases such as pepsin. In general, MNs can create micron-size channels, overcome the stratum corneum barrier, and deliver therapeutic proteins efficiently. Here, we designed hydrogel-based MNs to deliver catalase protein efficiently. For the fabrication of hydrogel-based MNs, the first step was to produce a MN master mold by using a 3D printer. The second step was to generate a polydimethylsiloxane (PDMS) mold by the reverse micro-molding technique. Next, a hydrogel solution with polyvinyl alcohol (PVA) and chitosan was optimized to produce casted hydrogel MN embraced with good mechanical properties. Among the ratio of PVA to chitosan used in the MN fabrication, the 2:1 ratio (w/w) of PVA:chitosan was the optimized composition for attaining ideal morphology and mechanical strength. Catalase was subsequently loaded onto the hydrogel MNs, and it was successfully delivered into the pig ear through passive diffusion. A longer residence time until 1 h improved the delivery of catalase that kept enzymatic activity after the delivery. Protein delivery using MNs was also strongly enhanced by external stimulations such as ethanol or ultrasound, which was known to disrupt the stratum corneum. The global market for MNs as a drug delivery system is ready to expand, and numerous applications of hydrogel-based MNs are anticipated to deliver therapeutic proteins.

Amyloid-β (Aβ) and islet amyloid polypeptide (IAPP) are small peptides that have the potential to not only self-assemble but also cross-assemble and form cytotoxic amyloid aggregates. Recently, we experimentally investigated the nature of Aβ-IAPP coaggregation and its inhibition by small polyphenolic molecules. Notably, we found that epigallocatechin gallate (EGCG) had the ability to reduce heteroaggregate formation. However, the precise molecular mechanism behind the reduction of heteroaggregates remains unclear. In this study, the dimerization processes of Aβ40 and IAPP peptides with and without EGCG were characterized by the enhanced sampling technique. Our results showed that these amyloid peptides exhibited a tendency to form a stable heterodimer, which represented the first step toward coaggregation. Furthermore, we also found that the EGCG regulated the dimerization process. In the presence of EGCG, well-tempered metadynamics simulation indicated a notable shift in the bound state toward a greater center of mass (COM) distance. Additionally, the presence of EGCG led to a significant increase in the free energy barrier height (∼15k B T) along the COM distance, and we observed a transition state between the bound and unbound states. Our findings also unveiled that the EGCG formed a greater number of hydrogen bonds with Aβ40, effectively obstructing the dimer formation. In addition, we carried out microseconds of all-atom conventional molecular dynamics (cMD) simulations to investigate the formation of both hetero- and homo-oligomer states by these peptides. MD simulations illustrated that EGCG played a significant role in preventing oligomer formation by reducing the content of β-sheets in the peptide. Collectively, our results offered valuable insight into the mechanism of cross-amyloid aggregation between Aβ40 and IAPP and the inhibition effect of EGCG on the heteroaggregation process.

Background Anthocyanins, one of the subclasses of flavonoids, are water-soluble phytochemicals and essential pigments in vegetables or fruits, and there is significant interest due to their potential health benefits. Anthocyanins have demonstrated anticancer effects such as inhibition of cell proliferation, and stimulation of apoptosis. Here, we investigated that anthocyanins could selectively inhibit the proliferation of breast cancer cells. Methods Anthocyanins were extracted from four different vegetables (red cabbage, red onion, black bean, and eggplant), and five different fruits (pomegranate, raspberry, blueberry, blackberry, and red grape), and cytotoxicity of all anthocyanins were measured. Results Among nine anthocyanins, blueberry anthocyanins were the best candidate to be toxic to only breast cancer cell lines such as MDA-MB-231 and MCF-7, but not to be toxic to other type of cells such as THP-1 and Caco-2 cell lines. From transwell cell migration assay, blueberry anthocyanins reduced the migration of MDA-MB-231 by 31.7%. 3D-cultured spheroid experiment demonstrated that blueberry anthocyanins reduced the cell density of spheroids, and enhanced the cell toxicity of spheroids. Conclusions The results of this research enhanced the understanding of the selective anticancer effect of blueberry anthocyanins on MDA-MB-231 and MCF-7 breast cancer cell lines.

The measurement of cell membrane potential (V m) is important for understanding ion channel function. V m plays a role in several routine cellular functions and diseases, particularly in excitable cells such as muscle and nerve. However, measuring V m is difficult, relying either on labour-intensive direct measurement of single cells (intracellular electrodes, patch clamp) or indirect measurement of fluorescence intensity, using V m-sensitive labels. Here we demonstrate a direct measurement technique based on determination of the cell's zeta-potential, the electrical potential at the hydrodynamic shear plane, approximately 1 nm beyond the cell surface. We demonstrate this principle using excitable H9c2 cardiomyoblasts, measured in both polarised and depolarised states, before and after extracellular intervention to alter cell ion concentration. Given widespread availability of zeta-potential measurement apparatus (most typically in chemistry and materials science settings), this offers a new method of measuring V m without the need for fluorescence measurements or calibration curves.

Smart contact lenses offer unique opportunities as personalized, non-invasive devices that simultaneously perform a wide range of functions. However, the actual production of smart contact lenses is rather challenging. Herein, two vat photopolymerization 3D printing techniques are presented for producing multimaterial and multifunctional contact lenses. In the first technique, a contact lens is 3D printed with hollow channels, which are later filled with resin containing different dyes or drugs. In the second method, functionalized structures are directly 3D printed on top of a commercial contact lens. Atto dyes enable red-green and blue-yellow color vision correction. Photochromic dye enables UV monitoring, warning the wearer in case of UV hazards. Multifunctional contact lenses which can perform ocular health monitoring can also be produced through these techniques. Drug delivery is explored from drug-loaded structures added on the contact lens. Herbal eye drops and phenol red were utilized for studying drug release. The dyes and drugs are incorporated into hydroxyethyl methacrylate and polyethylene glycol diacrylate (HEMA:PEGDA) hydrogels. Drug release rate can be varied by varying the drug loading or the hydrogel composition. The multifunctional contact lenses displayed excellent optical and material properties. Drug loaded structures are printed as peripheral structures that do not hinder vision. These multifunctional contact lenses can enable simultaneous color vision correction, health monitoring and drug delivery without disturbing the daily routine of the wearer. The study demonstrates the potential of vat photopolymerization 3D printing for cost-effective production of multifunctional contact lenses.

Long-term exposure to ultraviolet (UV) radiation causes severe illnesses like pterygium, cataracts, climatic droplet keratopathy, solar retinopathy, and uveal melanoma. Occupational UV exposure is a significant concern for arc welders, laboratory technicians, and laborers directly exposed to sunlight. Here, we report photochromic contact lenses that change color in the presence of UV radiation. In addition to offering UV blockage, these contact lenses alert the wearer to UV hazards. The usage of photochromic dyes for UV protection is relatively recent, and there is great scope for further research in this field. The 4D-printed contact lenses developed here present strong optical, mechanical, and water absorption properties in addition to quick color transition and UV-blocking characteristics. Furthermore, multimaterial contact lenses with UV- monitoring rings enable smart monitoring and reporting of UV exposure incidents. These contact lenses can ensure better workplace safety by alerting and protecting individuals.

MXenes, is an attractive new class of two-dimensional (2D) materials, discovered in 2011. Since then, owing to their unique combination of properties, such as high specific area, high electrical conductivity, tunable hydrophilicity, tunable chemical composition, and potential cytocompatibility, MXenes have made a deep impact on various fields ranging from electronics to energy and more recently to biotechnology. A typical example for the latter, is their use as electroactive biointerfaces in a number of biosensor setups, exhibiting remarkable analytical performance. In particular, MXene-based nanocomposites can serve as bioreceptors, electrochemical transducers or amplification probes towards translating molecular recognition of biological targets into detectable signals, leading to ultrasensitive biosensors for probing biomarkers, or pathogens. This concise review highlights the recent advances of MXene-based electrochemical biosensors for highly selective and sensitive detection of nucleic acids, proteins and pathogens pertaining to biomarker identification and clinical diagnostics. In particular, the effects of synthetic routes, surface chemistry, nanocomposite design, and fabrication methods of MXenes on the resulting relationship between biointerfacial structure, electrochemical properties and device performance is discussed, providing unique perspectives and design criteria for the next wave of biosensors.

Oxidative stress, i.e., excessive production of reactive oxygen species (ROS), plays an important role in the pathogenesis of inflammatory diseases such as cardiovascular diseases, cancer, and neurodegenerative diseases. Catalase, an antioxidant enzyme, has great therapeutic potential; however, its efficacy is limited by its delivery to target cells or tissues. In order to achieve efficient delivery, consistent drug distribution, and drug activity, small and uniformly sized drug delivery vehicles are needed. Here, three-dimensional (3D) microcubes were printed by Nanoscribe Photonic Professional GT2, a high-resolution 3D printer, and the characteristics of 3D-printed microcubes as drug delivery vehicles for the delivery of catalase were investigated. The size of the 3D-printed microcubes was 800 nm in length of a square and 600 nm in height, which is suitable for targeting macrophages passively. Microcubes were also tunable in shape and size, and high-resolution 3D printing could provide microparticles with little variation in shape and size. Catalase was loaded on 3D-printed microcubes by nonspecific adsorption, and catalase on 3D-printed microcubes (CAT–MC) retained 83.1 ± 1.3% activity of intact catalase. CAT–MC also saved macrophages, RAW 264.7, from the cytotoxicity of H2O2 by 86.4 ± 4.1%. As drug delivery vehicles, 3D-printed microparticles are very promising due to their small and uniform size, which provides consistent drug distribution and drug activity. Therefore, we anticipate numerous applications of 3D-printed microparticles for delivering therapeutic proteins.

Transforming growth factor β1 (TGF-β1) is critical to cell differentiation, proliferation, and apoptosis. It is important to understand the binding affinity between TGF-β1 and its receptors. In this study, their binding force was measured using an atomic force microscope. Significant adhesion was induced by the interaction between the TGF-β1 immobilized on the tip and its receptor reconstituted in the bilayer. Rupture and adhesive failure occurred at a specific force around 0.4~0.5 nN. The relationship of the force to loading rate was used to estimate the displacement where the rupture occurred. The binding was also monitored in real time with surface plasmon resonance (SPR) and interpreted with kinetics to acquire the rate constant. Using the Langmuir adsorption, the SPR data were analyzed to estimate equilibrium and association constants to be approximately 107 M−1 and 106 M−1 s−1. These results indicated that the natural release of the binding seldom occurred. Furthermore, the degree of binding dissociation, confirmed by the rupture interpretation, supported that the reverse of the binding hardly happened.

Color blindness or color vision deficiency (CVD) is a congenital ocular deficiency that hampers patients' daily life activities. CVD patients rely mostly on using wearable visual aids that enhance color distinction by blocking problematic wavelengths of light. Contributing to that, this study examines the fabrication of 3D-printed colored contact lens for color blindness management. A vat photopolymerization based 3D printing technology is utilized to fabricate the contact lenses for CVD patients. An in-house prepared resin is mixed with a low-cost colored ink to attain the desired blocking range (520-580 nm). The fabricated lens blocks more than 50% of light at the problematic wavelengths, along with exhibiting minimal leakage when stored and examined in water and contact lens storage solution. Average contact angle and water content values are 48 degrees and 56%, respectively. Mechanical properties demonstrate the physical adequacy of the contact lens. The CVD filtering efficacy of the tinted contact lens and its potential as a CVD wearable is evaluated by comparing its optical performance with that of commercial products. Finally, cytotoxicity analysis of the lens to dermal fibroblast cells reveals the biocompatibility of the lens as the cell viability remains greater than 75% after 24 h.

We examine numerically the feasibility of using a relatively new solitary wave-based non-destructive test (NDT) method for site-specific bone quality assessment. Towards this end, we present numerical predictions of the effective elastic modulus of trabecular bone in the proximal femur using highly nonlinear solitary waves (HNSWs) propagating in a one-dimensional chain of spherical steel particles. A computational bone reconstruction technique, enabled through topology optimization, is developed to generate high-resolution finite-element models representing the complex architecture of the trabecular network in the femoral neck region of the proximal femur. The reconstructed bone microstructure models are then used as the inspection medium in a virtual NDT setup in the form of a hybrid discrete-element/finite-element (DE/FE) model, capable of simulating the propagation of HNSWs in the granular chain and their interaction with the bone microstructures. By inserting a face sheet between the granular chain and the porous trabecular bone model, our calculations evince that dynamic loading by the incident solitary wave results in nearly uniaxial deformation of the bone microstructure (rather than localized contact indentations), and this is shown to enhance the accuracy and reliability of the solitary wave-based prediction of the bone's effective elastic modulus. Using the delay of the primary reflected solitary wave in the estimation of the elastic modulus of bone, we are able to estimate the effective elastic moduli of the porous bone models with adequate accuracy. Based on these numerical findings, we believe that solitary wave-based non-destructive evaluation of computationally reconstructed artificial bone models could form the baseline for advanced bone quality assessment tools.

Amyloid β (Aβ) and islet amyloid peptide (IAPP) are small peptides, that have potential to self-assemble and form cytotoxic aggregates. The self-aggregation of Aβ peptide accelerates the progression of Alzheimer's disease (AD), whereas IAPP aggregates stimulate the apoptosis in pancreatic β cells, which leads to type 2 diabetes (T2D). Several studies have confirmed co-deposition of Aβ and IAPP in both brain and pancreatic tissues. This co-deposition suggests that Aβ-IAPP cross-interactions might be the principal factors that connect AD and T2D at molecular level. Recently, we studied the nature of Aβ-IAPP co-aggregation and its inhibition by small molecules experimentally. We selected the polyphenolic candidates to inhibit the IAPP or Aβ self-aggregation and examined the inhibitory effects of most potential candidates on Aβ-IAPP co-aggregation. We found that epigallocatechin gallate (EGCG) reduces the hetero-aggregate formation. However, the molecular mechanism behind the hetero-aggregate reduction remains elusive. Here, in this study, we used all-atom molecular dynamics simulations to investigate the molecular mechanism for the co-aggregation of Aβ-IAPP with and without EGCG. Our simulation results suggest that peptides in the mixture tend to form heterodimers as the first step toward their coaggregation. Metadynamics simulations allowed us to compute the free energy surface of the heterodimers, providing a direct comparison between the experiments and simulations. Molecular simulations show good agreement with experiments both in the presence and absence of EGCG. We found that the unfolding of Aβ contributes to the aggregation whereas EGCG prevents Aβ unfolding. In addition, we also investigated the formation of hexamers by these peptides and established links between the monomer configuration and the oligomer state. The hot spot regions of the two amyloid peptides were studied to understand the hexamer formation in a hetero and homogeneous peptide environment.

To date, more than 37 amyloidogenic proteins have been found to form toxic aggregates that are implicated in the progression of numerous debilitating protein misfolding diseases including Alzheimer's disease (AD). Extensive literature highlights the role of β-amyloid (Aβ) aggregates in causing excessive neuronal cell loss in the brains of AD patients. In fact, major advances in our understanding of Aβ aggregation process, including kinetics, toxicity, and structures of fibrillar aggregates have been revealed by examining in vitro preparations of synthetic Aβ peptides. However, ongoing research shows that brain-derived Aβ aggregates have specific characteristics that distinguish them from in vitro prepared species. Notably, the molecular structures of amyloid fibrils grown in the human brain were found to be markedly different than synthetic Aβ fibrils. In addition, recent findings report the existence of heterogeneous Aβ proteoforms in AD brain tissue in contrast to synthetically produced full-length aggregates. Despite their high relevance to AD progression, brain-derived Aβ species are less well-characterized compared with synthetic aggregates. The aim of this review is to provide an overview of the literature on brain-derived Aβ aggregates with particular focus on recent studies that report their structures as well as pathological roles in AD progression. The main motivation of this review is to highlight the importance of utilizing brain-derived amyloids for characterizing the structural and toxic effects of amyloid species. With this knowledge, brain-derived aggregates can be adopted to identify more relevant drug targets and validate potent aggregation inhibitors toward designing highly effective therapeutic strategies against AD.