Extracellular vesicles (EVs) have gained recognition as crucial mediators of cell-to-cell communication, holding immense potential in diverse biomedical applications. Nanoarchitectonics, a multidisciplinary approach encompassing nanotechnology and biomedicine, offers novel strategies for manipulating EVs at the nanoscale. This review explores the transformative influence of nanoarchitectonics on EVs research, focusing on the current progress in integrating various nanostructures to engineer EVs for enhanced therapeutic and diagnostic capabilities. The application of nanoarchitectonics has led to the fabrication of specialized nanostructures, such as plasmonic, fluorescent, magnetic, carbon-based, and organic-framework-based nanostructures designed explicitly for EVs research. This approach enables the engineering of EVs with improved targeting specificity, cargo loading efficiency, and therapeutic efficacy, thus advancing their potential in precision medicine. The review addresses the opportunities and challenges associated with the convergence of nanoarchitectonics and EVs research, underscoring the necessity for further optimization, rigorous safety assessments, and interdisciplinary collaboration. Finally, the review concludes by discussing the strengths and limitations of the nanoarchitectonics-EVs interface in nanomedicine and therapeutics, providing a strategic roadmap for future advancements in this rapidly evolving field.
Mesoporous gold and silver films on copper (Mp-Au/Cu and Mp-Ag/Cu) are fabricated via a micelle-templated electroless displacement deposition. This one-step, substrate-flexible method generates uniform, highly porous metallic films with excellent adhesion and scalability. Electron microscopy results reveal well-defined nanoscale pores with mean diameters of ∼25 nm for Mp-Au/Cu and ∼16 nm for Mp-Ag/Cu, resulting in large specific surface areas and densely distributed plasmonic hotspots. Structural analyses confirm nanocrystalline metallic domains and high purity of the mesoporous networks. The open porous architecture provides a stable and biocompatible interface, facilitating efficient immobilisation of biomolecules and enabling functional bio-conjugation. As a proof-of-concept demonstration, Mp-Au/Cu films are employed as surface-enhanced Raman scattering (SERS) substrates for the detection of the pro-inflammatory cytokine interleukin-1β (IL-1β). The mesoporous framework promotes precise localisation of DTNB-encoded, antibody-conjugated SERS nanotags within plasmonic hotspots, producing intense and photostable Raman signals. The platform exhibits excellent reproducibility (RSD = 3.8%), nearly two-fold enhancement compared to flat Au controls, and a low detection limit of 17.6 pg mL-1. Control experiments confirm high selectivity and minimal nonspecific binding. Collectively, these findings introduce Mp-Au/Cu as a robust, sensitive, and biofunctional plasmonic material capable of highly reproducible cytokine detection, providing a versatile foundation for next-generation biosensing and diagnostic technologies.
Cancer remains one of the leading causes of mortality worldwide, necessitating the development of advanced diagnostic and therapeutic strategies with improved specificity, safety and efficacy. Carbon quantum dots (CQDs) have emerged as a versatile class of nanomaterials with unique optical, physicochemical, and biocompatible properties suitable for biomedical applications. Recently, bioinspired carbon quantum dots (B-CQDs) derived from medicinal plants have gained considerable attention as sustainable and functional nanomaterials for cancer management. This review critically examines the synthesis approaches, physicochemical properties, biological activities and anti-cancer potential of B-CQDs including biosensing, bioimaging, drug delivery, and photo-induced therapies. Current literature reveals that B-CQDs can induce reactive oxygen species (ROS) mediated cytotoxicity, facilitate specific cellular uptake and accelerate photodynamic therapeutic effects, emerging their role in cancer diagnostics and therapeutics. However, recent reports demonstrated that biological activities are interpreted through a precursor-centric framework, in which medicinal plant origin is presumed to control bioactivity. Moreover, surface physicochemical properties primarily influence biological activity while precursor effects are indirect and synthesis dependent. Current challenges including reproducibility, regulatory approval standardization and intellectual property protection sustain limitations on clinical translation and commercialization. Future investigations should uncouple precursor effects from surface chemistry and combine with advanced mechanistic quantitative structure characterization analysis. This will facilitate the rationale-driven design of B-CQDs for clinical application toward precision oncology diagnostics and treatment.
Ovarian cancer is one of the leading causes of gynecologic cancer-related mortality in women. However, a significant proportion of ovarian cancer cases are only detected at an advanced stage (III or IV) and are complicated to treat because of metastasis to the peritoneum. This challenge is compounded by vague symptoms and insufficient screening methods for early ovarian cancer detection. A promising solution is liquid biopsy, where the presence of biomarkers (proteins, lipids, and nucleic acids) associated with cancer is identified in the blood circulation. This approach facilitates the real-time monitoring of cancer progression and treatment effects in a non-invasive manner. This contrasts with traditional tumor biopsy, where only a small portion of the tumor is sampled, serial sampling of the tumor is impractical, or sometimes, tumor biopsy is not feasible. This review discusses the cell-free and extracellular vesicle components in blood, highlighting their DNA as a target in liquid biopsies for cancer diagnostics, with a specific emphasis on ovarian cancer. It also underscores the need for further research into the biological underpinnings and functional roles of these DNA fragments to integrate them into multi-omics approaches for detailed insights into tumor biology and treatment resistance in ovarian cancer.
Early detection of ovarian cancer in asymptomatic women is critical, as diagnosis at stages I-II is associated with >90% survival, whereas survival declines to 20-40% at stages III-IV.Tumor-derived extracellular vesicles...
Minimally invasive surgery (MIS) is a vital procedure for the treatment of several cardiac and neural diseases, such as clearing clogged arteries, pacing irregular heartbeats, monitoring intracranial pressure, and draining excess cerebrospinal fluid from the brain. Recent research advances in soft electronics demonstrate the potential of integrated electrodes in enhancing MIS performance, enabling in situ biopotential measurement, electrical stimulation, and bioimpedance sensing. The addition of these modalities expands the potential of MIS to deliver targeted cardiac interventions or further minimize risks through brain activity monitoring during the procedure. Existing sensor-integrated catheters still exhibit several drawbacks, such as a sizable increase in catheter profile, inconsistent electrode performance, limited fabrication scalability, and a lack of active steering capability. We report here the development of flexible electrodes using mesoporous gold as a functional layer with enhanced surface impedance characteristics for recording, high charge injection capacity for stimulation, and mechanical compliance for integration into a wide range of MIS tools with varied diameters. Integrating the electrode into a soft robotic catheter driven by an embedded microfluidic channel and microtubing demonstrates a manoeuvrable system with electrical and mechanical stability under various bending conditions, together with a low system profile suitable for a minimally invasive procedure. Through a set of ex vivo and in vitro experiments, we demonstrate the potential of our system for various biomedical applications, including field potential measurement, bioimpedance sensing, and cardiac pacing, that can leverage the capability of MIS procedures.
Industry-relevant, hands-on training is critical in undergraduate bioprocess engineering education. This article emphasizes the benefits of active learning in industry-relevant safety regulations, facilities, equipment, processes, and products. The course tasks students to produce and analytically assess the properties of beer in a pilot-scale, food-grade, university facility (microbrewery). In addition to being an educational space, the microbrewery also serves as a research facility, enabling research-informed and industry-facing practical training. Students also visit a large-scale commercial brewery to draw parallels between pilot and industry-scale beverage production. Similarities with other bioprocess engineering applications, such as those in the pharmaceutical industry, are emphasized. Subjective and objective results from anonymous surveys revealed that the industry-relevant practical components enhanced student engagement, career interests, and learning outcomes
Ovarian cancer is the most common gynaecological malignancy and the seventh most diagnosed cancer in females worldwide. Currently, it is the sixth leading cause of cancer related mortality among patients globally. The heterogenous origin of the disease and unambiguous nature of the clinical symptoms leading to delayed detection has been one of the key reasons for increasing mortality. Hence new approaches are required to understand the biology of ovarian cancer, where the use of cell culture models that mimic the physiology of the disease is fundamental. Cell culture serves as a crucial in vitro tool, contributing to our comprehension of various aspects of cell biology, tissue morphology, disease mechanisms, drug responses, protein production, and tissue engineering. A significant portion of in vitro studies rely on two-dimensional (2D) cell cultures, however, these cultures present notable limitations, for example disruptions in cellular and extracellular interactions, alterations in cell morphology, polarity, and division mechanisms. Recently, extracellular vesicles have been identified as crucial players in cell biology as part of the communication system that cancer cells use to metastasize. We optimized and compared three-dimensional (3D) culture of ovarian cancer cells lines (SKOV-3 and OVCAR-3) with two-dimensional models based on their protein and miRNA content. We further investigated whether extracellular vesicles from these models reflect changes in cancer cells, and aid in the identification of overall survival in women with ovarian cancer.
Extracellular vesicles (EVs) are lipids bilayer-delimited particles carrying bioactive molecules such as proteins, lipids, and nucleic acids, reflecting the physiological state of their origin. Found in biofluids like saliva, urine, blood, and peritoneal fluid, EVs serve as promising minimally invasive biomarkers for several conditions including cancer. However, achieving high sensitivity and specificity in EV detection remains technically challenging. Placental Alkaline Phosphatase (PLAP), an enzyme primarily expressed in the placenta during pregnancy, has emerged as a clinically relevant biomarker in gynecological malignancies, including ovarian cancer (OC). In this study, a nanoengineered mesoporous gold (mAu)-based Surface-Enhanced Raman Spectroscopy (SERS) platform is reported for the rapid and ultrasensitive detection of PLAP-positive EVs in OC patients. The mAu offers high surface roughness, enabling numerous localized plasmonic hotspots that amplify Raman signals and improve probe and antibody loading. This allowed the detection of as few as 100 EVs mL-1 with excellent reproducibility (RSD < 5%,n = 3). In clinical validation (n = 30), the assay achieved 90% sensitivity (95% CI: 60%-100%) and 85% specificity (95% CI: 15%-100%) in distinguishing OC patients from those with benign and healthy controls, demonstrating superior performance compared to CA-125. The mAu-SERS platform shows considerable promise as a minimally invasive and clinically applicable diagnostic strategy for OC, especially for differential diagnosis for their ability to distingluis between benign and OC conditions.
High-grade serous ovarian cancer (HGSOC) is a highly aggressive malignancy often diagnosed at an advanced stage due to the absence of early symptoms and effective diagnostic tools. Extracellular vesicles (EVs) secreted by tumour cells carry disease-specific biomarkers, offering potential for early detection. However, their low concentration in biological samples poses challenges for isolation and detection, necessitating highly sensitive and specific multiplexed assays for subsequent detection of multiple biomarkers. Herein, we report the design of metal-organic framework (MOF)-derived porous superparamagnetic iron oxide nanorods (MOF-IONRs) to construct a rapid and sensitive surface-enhanced Raman scattering (SERS)-based multiplexed assay to detect HGSOC-specific EV protein biomarkers in clinical samples. The high porosity and large surface area of MOF-IONRs enable enhanced antibody loading and efficient biomarker capture, while simultaneously enriching SERS nanotags for signal amplification. Their intrinsic magnetic properties facilitate straightforward magnet-based isolation and purification of EVs. Additionally, the incorporation of mesoporous gold nanoparticle (mAuNP)-based SERS nanotags further enhance the Raman signal intensity. This integrated platform exhibits a limit of detection (LoD) of 2.13 EVs per µL with excellent reproducibility (%RSD < 10%, n = 3). Clinical validation successfully distinguishes ovarian cancer patients from healthy controls, highlighting its diagnostic accuracy and reliability. This multiplexed platform shows promise as a liquid biopsy for the early diagnosis of HGSOC, enabling rapid, cost-effective, and highly sensitive detection of EV-associated biomarkers in complex clinical samples. Moreover, integration with a handheld Raman spectrometer provides portability and compatibility with point-of-care (POC) testing, highlighting its promise as a transformative tool in ovarian cancer diagnostics and patient management.
Immune checkpoint proteins (ICPs) play a critical role in tumor immune evasion and have emerged as key biomarkers for cancer diagnosis, treatment selection, and monitoring immunotherapy responses, particularly in lung cancer. Frequent assessment of ICP expression is essential for guiding therapeutic decisions and evaluating treatment efficacy. Extracellular vesicles (EVs), secreted into the bloodstream by cancer cells, mirror the molecular profile of their cells of origin, including surface-expressed ICPs, offering a minimally invasive window into tumor biology. However, conventional assays lack the sensitivity and specificity to detect ICPs on heterogeneous EV populations. Here, we present a highly sensitive and integrated biosensing platform based on surface-enhanced Raman scattering (SERS) coupled with a nanostructured mesoporous gold (Au) chip for multiplexed detection of ICPs on lung cancer-derived EVs. The platform incorporates an anti-EGFR-functionalized mesoporous Au surface to selectively capture tumor-derived EVs and utilizes SERS nanotags for the simultaneous detection of four key ICPs: PD-L1, B7H4, CD276, and CD80. The highly ordered and densely packed pores of the 3D mesoporous Au nanostructure increase the surface area for antibody immobilization, while simultaneously amplifying SERS signal intensity through localized plasmonic hotspots, together enabling ultra-sensitive and highly specific detection of EV associated biomarkers. Using EVs derived from the HCC827 lung cancer cell line, our platform successfully identified target EVs within a complex background and profiled ICP expression patterns. Notably, CD276, PD-L1, and B7H4 exhibited dominant expression on EV surfaces, with marked alterations in their levels following EGFR inhibitor treatment, highlighting the dynamic nature of immune modulation in response to therapy. These findings underscore the clinical utility of the mesoporous Au-integrated SERS platform for non-invasive lung cancer diagnostics and longitudinal monitoring of immunotherapy-induced immune modulation.
Herein, we developed a specific, rapid sensor to quantify placental extracellular vesicle (EV) protein biomarkers of early pregnancy complications. A distinct tetraspanin CD9 and placental alkaline phosphatase (PLAP) expression pattern was observed via targeted multiple reaction monitoring of EVs from maternal plasma collected before 18 weeks of gestation. A classification model was developed using training and validation patient sets, distinguishing between individuals at high risk of developing complications from those with normal pregnancies, achieving 80% sensitivity, 90% specificity, 89% positive predictive value (PPV), and 82% negative predictive value (NPV). Superparamagnetic nanoflowers that captured target EVs (CD9+/PLAP+) were used to construct a 4-flex glass strip nanozymatic readout system. The sensor analyzes plasma for EVs, identifying gestational diabetes mellitus risk with a 95% combined sensitivity, 100% specificity, 100% PPV, and 96% NPV. This nanoplatform identifies individuals at risk of developing pregnancy complications with a >90% classification accuracy, exhibiting potential for clinical applications.
We report the synthesis of nanoporous Pt–Pd thin layers on silica spheres. Amino-functionalized beads improve metal ion adhesion, enabling crack-free nanoporous layers via electroless deposition with a surfactant template.
The use of nanomaterials is an exciting prospect to facilitate radiotherapy delivery based on molecular targeting of tumors. This molecular targeted radiotherapy approach involves the use of radioligands-radioactive isotopes that are chemically linked to tumor-binding ligands–to ensure that radiation damage is delivered accurately and efficiently to tumor cells while sparing normal tissues. Although the use of nanomaterials has been well summarized for passive cancer radiotherapy, a clinical take on modern molecular targeted radioligand applications is yet to be reviewed. In this review, we will firstly discuss the innovative design of nanomaterials in relation to pre-clinical molecular targeted radioligand therapy. As we identify a current lack of clinical nanomaterial-based radiotherapy across various tumor types, we then provide our insights on related challenges and strategies to clinically translate innovative nanomaterial technologies to aid in driving molecular targeted radioligand therapies.
The rapid rise of antibiotic-resistant bacteria (ABR) presents an urgent global health challenge, necessitating the development of efficient and scalable diagnostic technologies. Electrochemical biosensors have emerged as a promising solution, offering high sensitivity, specificity, and adaptability for point-of-care applications. These innovative platforms utilize bio-recognition elements, advanced electrode materials, microbial enzymes, and redox-active metabolites to identify antibiotic resistance profiles at a molecular level. Recent progress in microfluidics and lab-on-a-chip systems has enabled real-time, high-throughput antimicrobial susceptibility testing, significantly improving diagnostic precision and speed. This review aims to critically evaluate recent advances in electrochemical biosensing strategies for detecting ABR, identify key challenges, and propose future directions to enhance clinical applicability. Key developments include bio-receptor-based detection strategies, novel electrode surfaces, and multiplexed platforms integrated with microfluidic systems. Additionally, this review examines essential biomarkers for detecting antibiotic resistance and explores key challenges, including variability in biomarker expression and sensor reproducibility. It also highlights practical barriers to clinical implementation, such as cost constraints and scalability concerns. By presenting innovative approaches, such as cost-effective material alternatives, advanced analytical techniques, and portable biosensing systems, this review outlines a strategic pathway for enhancing the accessibility and effectiveness of electrochemical biosensors in antibiotic resistance management.
This study reports a one-step electrodeposition of ternary mesoporous gold-silver-copper (mAuAgCu) alloy films by using diblock copolymers as pore-directing agents. Additionally, it examines the effects of alloy composition on the electrocatalytic performance of mAuAgCu thin films. Using advanced characterization techniques, such as scanning transmission electron microscopy and X-ray photoelectron spectroscopy, the interplay between alloy composition, surface structure, and catalytic performance is revealed. The optimized mAu(0.60)Ag(0.20)Cu(0.20) alloy (prepared from the precursor solution with an Au:Ag:Cu ratio of 60:20:20) demonstrates the highest catalytic activity for glucose sensing. This is because the introduction of Cu facilitates a uniform distribution of defects in this mesoporous ternary alloy through controlled reduction, leading to a higher electrochemically active surface area (ECSA) and more active sites for electrochemical reactions. This research provides valuable insights into designing trimetallic alloys, demonstrating how the surface structure and alloy composition can control the catalytic performance for electrochemical applications.
Pseudomonas aeruginosa is a high-risk pathogen associated with several human diseases. Pyocyanin (PYO), a redox-active secondary metabolite produced by P. aeruginosa, plays a critical role in its survival and pathogenicity, exhibiting both antibacterial and toxic properties. Recent studies have shown that reducing PYO production can inhibit the growth of P. aeruginosa. Here, we report the extraction of cellulose nanocrystals from rice husk for the fabrication of cellulose nanocrystal/polypyrrole (PPy/cellulose) composite disks. This nanocomposite disk acts as a simple, highly efficient, and cost-effective adsorbent for removing PYO metabolites from contaminated water samples. The chemical and morphological features of the PPy/cellulose composites are investigated using various techniques. Solid-phase extraction is employed to remove PYO, with treatment conditions optimized for maximum efficiency. Both two-parameter and three-parameter models are used to analyze the equilibrium data for PYO removal. The optimal adsorbent dose is found to be 20 mg at 303 K for 35 minutes. The PPy/cellulose disk reaches maximum adsorption, removing over 93% of 10 ppm PYO. This approach presents a novel and effective strategy for mitigating the harmful effects of PYO, with potential applications in treating P. aeruginosa infections and recycling PYO for antimicrobial use.
Lattice strain effects on the piezoelectric properties of crystalline ferroelectrics have been extensively studied for decades; however, the strain dependence of the piezoelectric properties at nano-level has yet to be investigated. Herein, a new overview of the super-strain of nanoporous polycrystalline ferroelectrics is reported for the first time using a nanoengineered barium calcium zirconium titanate composition (Ba0.85Ca0.15)(Ti0.9Zr0.1)O3 (BCZT). Atomic-level investigations show that the controlled pore wall thickness contributes to highly strained lattice structures that also retain the crystal size at the optimal value (<30 nm), which is the primary contributor to high piezoelectricity. The strain field derived from geometric phase analysis at the atomic level and aberration-corrected high-resolution scanning transmission electron microscopy (STEM) yields of over 30% clearly show theoretical agreement with high piezoelectric properties. The uniqueness of this work is the simplicity of the synthesis; moreover the piezoresponse d 33 becomes giant, at around 7500 pm V-1. This response is an order of magnitude greater than that of lead zirconate titanate (PZT), which is known to be the most successful ferroelectric over the past 50 years. This concept utilizing nanoporous BCZT will be highly useful for a promising high-density electrolyte-free dielectric capacitor and generator for energy harvesting in the future.
Infectious diseases, particularly those caused by pathogens and parasites, present significant global health challenges. Despite advancements in medicine, these diseases continue to result in high rates of illness, loss of function, and mortality. The continuous COVID-19 pandemic, stemming from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the critical necessity for early detection strategies to improve patient outcomes. We present a novel microfluidics platform for the simultaneous detection of proteins (antigens) crucial for SARS-CoV-2 identification: S1, RBD, and NCD. By combining microfluidics with surface-enhanced Raman scattering (SERS), the platform enables highly sensitive and multiplexed detection of viral proteins. Furthermore, it employs an engineered mesoporous gold nanoparticle (mAuNP)-based SERS nanotags to achieve a highly sensitive readout. Demonstrating excellent analytical performance, our platform simultaneously detects three antigens, achieving detection levels as low as 14 pg mL(-1), with an RSD of <5.0% (n = 3). Compared to existing approaches, our platform offers critical improvements for SARS-CoV-2-like infectious disease analysis. It provides a multiplex detection system alongside controls, a simple experimental setup, and a single-device-based complete assay platform. The mAuNP-based SERS nanotags eliminate the need for enzymatic amplification, while the portable SERS readout facilitates an on-site detection without sophisticated instrumentation or laboratory requirements.