Amino-modified IONPs potentiates ferroptotic cell death due to the release of Fe ion in the lysosome.

Iron oxide nanoparticles (IONPs) have wide applications in the biomedical field due to their outstanding physical and chemical properties. However, the potential adverse effects and related mechanisms of IONPs in human organs, especially the lung, are still largely ignored. In this study, we found that group-modified IONPs (carboxylated, aminated and silica coated) induce slight lung cell damage (in terms of the cell cycle, reactive oxygen species (ROS) production, cell membrane integrity and DNA damage) at a sublethal dosage. However, aminated IONPs could release more iron ions in the lysosome than the other two types of IONPs, but the abnormally elevated iron ion concentration did not induce ferroptosis. Intriguingly, amino-modified IONPs aggravated the accumulation of intracellular peroxides induced by the ferroptosis activator RSL3 and thus caused ferroptosis in vitro, and the coadministration of amino-modified IONPs and RSL3 induced more severe lung injury in vivo. Therefore, our data revealed that the surface functionalization of IONPs plays an important role in determining their potential pulmonary toxicity, as surface modification influences their degradation behavior. These results provide guidance for the design of future IONPs and the corresponding safety evaluations and predictions.

3D Printing in Biocatalysis and Biosensing: From General Concepts to Practical Applications.

3D printing has matured into a versatile technique that offers researchers many different printing methods and materials with varying properties. Nowadays, 3D printing is deployed within a myriad of different applications, ranging from chemistry to biotechnology - including bioanalytics, biocatalysis or biosensing. Due to its inherent design flexibility (which enables rapid prototyping) and ease of use, 3D printing is facilitating the relatively quick and easy creation of new devices with unprecedented functions. This review article describes how 3D printing can be employed for research in the fields of biochemistry and biotechnology, and specifically for biocatalysis and biosensor applications. We survey different relevant 3D printing techniques, as well as the surface activation and functionalization of 3D-printed materials. Finally, we show how 3D printing is used for the fabrication of reaction ware and enzymatic assays in biocatalysis research, as well as for the generation of biosensors using aptamers, antibodies, and enzymes as recognition elements.

Base-free trifluoroacetylation: From methyl glucopyranoside to cellulose nanofibers.

Trifluoroacetic anhydride (TFAA) reacts smoothly with low molecular weight carbohydrates and cellulose nanofibers (CNFs) under base-free conditions. Methyl α- and ß-d-glucopyranoside were used as model compounds to optimize reaction conditions, which were then applied to lyophilized CNFs for surface modification. ATR-IR spectroscopy and powder X-ray diffraction were employed to characterize the modified CNFs. Trifluoroacetylation for 4 h yields a degree of substitution (DS) of 0.4 acyl groups per anhydroglucose unit while maintaining a crystallinity index near 50 %. DS values were quantified by gravimetry, acid-base titration after saponification, and a novel approach utilizing solution 19F NMR spectroscopy which offers greater accuracy than the other techniques. This study presents an efficient, base-free method for derivatizing carbohydrates as well as surface functionalization of CNFs with trifluoroacetyl groups, potentially expanding their application in fiber-reinforced thermoplastic composites.

Silk Fabric Functionalized by Nanosilver Enabling the Wearable Sensing for Biomechanics and Biomolecules.

Integrating biomechanical and biomolecular sensing mechanisms into wearable devices is a formidable challenge and key to acquiring personalized health management. To address this, we have developed an innovative multifunctional sensor enabled by plasma functionalized silk fabric, which possesses multimodal sensing capabilities for biomechanics and biomolecules. A seed-mediated in situ growth method was employed to coat silver nanoparticles (AgNPs) onto silk fibers, resulting in silk fibers functionalized with AgNPs (SFs@Ag) that exhibit both piezoresistive response and localized surface plasmon resonance effects. The SFs@Ag membrane enables accurate detection of mechanical pressure and specific biomolecules during wearable sensing, offering a versatile solution for comprehensive personalized health monitoring. Additionally, a machine learning algorithm has been established to specifically recognize muscle strain signals, potentially extending to the diagnosis and monitoring of neuromuscular disorders such as amyotrophic lateral sclerosis (ALS). Unlike electromyography, which detects large muscles in clinical medicine, sensing data for tiny muscles enhance our understanding of muscle coordination using the SFs@Ag sensor. This detection model provides feasibility for the early detection and prevention of neuromuscular diseases. Beyond muscle stress and strain sensing, biomolecular detection is a critical addition to achieving effective health management. In this study, we developed highly sensitive surface-enhanced Raman scattering (SERS) detection for wearable health monitoring. Finite-difference time-domain numerical simulations ware utilized to analyze the efficacy of the SFs@Ag sensor for wearable SERS sensing of biomolecules. Based on the specific SERS spectra, automatic extraction of signals of sweat molecules was also achieved. In summary, the SFs@Ag sensor bridges the gap between biomechanical and biomolecular sensing in wearable applications, providing significant value for personalized health management.

Click-Chemistry-Enabled Functionalization of Cellulose Nanocrystals with Single-Stranded DNA for Directed Assembly.

Controlling the self-assembly of cellulose nanocrystals (CNCs) requires precise control over their surface chemistry for the directed assembly of advanced nanocomposites with tailored mechanical, thermal, and optical properties. In this work, in contrast to traditional chemistries, we conducted highly selective click-chemistry functionalization of cellulose nanocrystals with complementary DNA strands via a three-step hybridization-guided process. By grafting terminally functionalized oligonucleotides through copper-free click chemistry, we successfully facilitated the assembly of brushlike DNA-modified CNCs into bundled nanostructures with distinct chiral optical dichroism in thin films. The complexation behavior of grafted DNA chains during the evaporation-driven formation of ultrathin films demonstrates the potential for mediating chiral interactions between the DNA-branched nanocrystals and their assembly into chiral bundles. Furthermore, we discuss the future directions and challenges that include new avenues for the development of functional, responsive, and bioderived nanostructures capable of dynamic reconfiguration via selective complexation, further surface modification strategies, mitigating diverse CNC aggregation, and exploring environmental conditions for the CNC-DNA assembly.

Site-Selective Biofunctionalization of 3D Microstructures Via Direct Ink Writing.

Two-photon lithography has revolutionized multi-photon 3D laser printing, enabling precise fabrication of micro- and nanoscale structures. Despite many advancements, challenges still persist, particularly in biofunctionalization of 3D microstructures. This study introduces a novel approach combining two-photon lithography with scanning probe lithography for post-functionalization of 3D microstructures overcoming limitations in achieving spatially controlled biomolecule distribution. The method utilizes a diverse range of biomolecule inks, including phospholipids, and two different proteins, introducing high spatial resolution and distinct functionalization on separate areas of the same microstructure. The surfaces of 3D microstructures are treated using bovine serum albumin and/or 3-(Glycidyloxypropyl)trimethoxysilane (GPTMS) to enhance ink retention. The study further demonstrates different strategies to create binding sites for cells by integrating different biomolecules, showcasing the potential for customized 3D cell microenvironments. Specific cell adhesion onto functionalized 3D microscaffolds is demonstrated, which paves the way for diverse applications in tissue engineering, biointerfacing with electronic devices and biomimetic modeling.

Detection of Sulfonamide Antibiotics Using an Elastic Hydrogel Microparticles-Based Optical Biosensor.

Sulfonamide antibiotics were the first synthetic antibiotics on the market and still have a broad field of application. Their extensive usage, wrong disposal, and limited degradation technologies in wastewater treatment plants lead to high concentrations in the environment, resulting in a negative impact on ecosystems and an acceleration of antibiotic resistance. Although lab-based analytical methods allow for sulfonamide detection, comprehensive monitoring is hampered by the nonavailability of on-site, inexpensive sensing technologies. In this work, we exploit functionalized elastic hydrogel microparticles and their ability to easily deform upon specific binding with enzyme-coated surfaces to establish the groundwork of a biosensing assay for the fast and straightforward detection of sulfonamide antibiotics. The detection assay is based on sulfamethoxazole-functionalized hydrogel microparticles as sensor probes and the biomimetic interaction of sulfonamide analytes with their natural target enzyme, dihydropteroate synthase (DHPS). DHPS from S. pneumoniae was recombinantly produced by E. coli and covalently coupled on a glass biochip using a reactive maleic anhydride copolymer coating. Monodisperse poly(ethylene glycol) hydrogel microparticles of 50 µm in diameter were synthesized within a microfluidic setup, followed by the oriented coupling of a sulfamethoxazole derivative to the microparticle surface. In proof-of-concept experiments, sulfamethoxazole, as the most used sulfonamide antibiotic in medical applications, was demonstrated to be specifically detectable above a concentration of 10 µM. With its straightforward detection principle, this assay has the potential to be used for point-of-use monitoring of sulfonamide antibiotic contaminants in the environment.

Functionalization of microbubbles in a microfluidic chip for biosensing application.

Microbubbles are widely used for biomedical applications, ranging from imagery to therapy. In these applications, microbubbles can be functionalized to allow targeted drug delivery or imaging of the human body. However, functionalization of the microbubbles is quite difficult, due to the unstable nature of the gas/liquid interface. In this paper, we describe a simple protocol for rapid functionalization of microbubbles and show how to use them inside a microfluidic chip to develop a novel type of biosensor. The microbubbles are functionalized with biochemical ligand directly at their generation inside the microfluidic chip using a DSPE-PEG-Biotin phospholipid. The microbubbles are then organized inside a chamber before injecting the fluid with the bioanalyte of interest through the static bubbles network. In this proof-of-concept demonstration, we use streptavidin as the bioanalyte of interest. Both functionalization and capture are assessed using fluorescent microscopy thanks to fluorescent labeled chemicals. The main advantages of the proposed technique compared to classical ligand based biosensor using solid surface is its ability to rapidly regenerate the functionalized surface, with the complete functionalization/capture/measurement cycle taking less than 10 min.

A surface-functionalized whole blood-based dielectric microsensor for assessment of clot firmness in a fibrinolytic environment.

Accurate assessment of fibrin clot stability can predict bleeding risk in coagulopathic conditions such as thrombocytopenia and hypofibrinogenemia. Hyperfibrinolysis - a clinical phenotype characterized by an accelerated breakdown of the fibrin clot - makes such assessments challenging by obfuscating the effect of hemostatic components including platelets or fibrinogen on clot stability. In this work, we present a biofunctionalized, microfluidic, label-free, electronic biosensor to elicit unique, specific, and differential responses from the multifactorial processes of blood coagulation and fibrinolysis ex vivo. The microsensor tracks the temporal variation in the normalized real part of the dielectric permittivity of whole blood (<10 µL) at 1 MHz as the sample coagulates within a three-dimensional, parallel-plate, capacitive sensing area. Surface biofunctionalization of the microsensor's electrodes with physisorption of tissue factor (TF) and aprotinin permits real-time assessment of the coagulation and fibrinolytic outcomes. We show that surface coating with TF and manual addition of TF result in a similar degree of acceleration of coagulation kinetics in human whole blood samples. We also show that surface coating with aprotinin and manual addition of aprotinin yield similar results in inhibiting tissue plasminogen activator (tPA)-induced upregulated fibrinolysis in human whole blood samples. Validated through a clinically relevant, complementary assay - rotational thromboelastometry for clot viscoelasticity - we finally establish that a microsensor dual-coated with both TF and aprotinin detects the hemostatic rescue in the tPA-induced hyperfibrinolytic profile of whole blood and the hemostatic dysfunction due to concurrent platelet depletion in the blood sample, thus featuring enhanced ability in evaluating complex, combinatorial coagulopathies.

A Descriptive Review on the Potential Use of Diatom Biosilica as a Powerful Functional Biomaterial: A Natural Drug Delivery System.

Although various chemically synthesized materials are essential in medicine, food, and agriculture, they can exert unexpected side effects on the environment and human health by releasing certain toxic chemicals. Therefore, eco-friendly and biocompatible biomaterials based on natural resources are being actively explored. Recently, biosilica derived from diatoms has attracted attention in various biomedical fields, including drug delivery systems (DDS), due to its uniform porous nano-pattern, hierarchical structure, and abundant silanol functional groups. Importantly, the structural characteristics of diatom biosilica improve the solubility of poorly soluble substances and enable sustained release of loaded drugs. Additionally, diatom biosilica predominantly comprises SiO2, has high biocompatibility, and can easily hybridize with other DDS platforms, including hydrogels and cationic DDS, owing to its strong negative charge and abundant silanol groups. This review explores the potential applications of various diatom biosilica-based DDS in various biomedical fields, with a particular focus on hybrid DDS utilizing them.

Magnetic Nanoparticles with On-Site Azide and Alkyne Functionalized Polymer Coating in a Single Step through a Solvothermal Process.

Background/Objectives: Magnetic Fe3O4 nanoparticles (MNPs) are becoming more important every day. We prepared MNPs in a simple one-step reaction by following the solvothermal method, assisted by azide and alkyne functionalized polyethylene glycol (PEG400) polymers, as well as by PEG6000 and the polyol ß-cyclodextrin (ßCD), which played a crucial role as electrostatic stabilizers, providing polymeric/polyol coatings around the magnetic cores. Methods: The composition, morphology, and magnetic properties of the nanospheres were analyzed using Transmission Electron and Atomic Force Microscopies (TEM, AFM), Nuclear Magnetic Resonance (NMR), X-ray Diffraction Diffractometry (XRD), Fourier-Transform Infrared Spectroscopy (FT-IR), Matrix-Assisted Laser Desorption/Ionization (MALDI) and Vibrating Sample Magnetometry (VSM). Results: The obtained nanoparticles (@Fe3O4-PEGs and @Fe3O4-ßCD) showed diameters between 90 and 250 nm, depending on the polymer used and the Fe3O4·6H2O precursor concentration, typically, 0.13 M at 200 °C and 24 h of reaction. MNPs exhibited superparamagnetism with high saturation mass magnetization at room temperature, reaching values of 59.9 emu/g (@Fe3O4-PEG6000), and no ferromagnetism. Likewise, they showed temperature elevation after applying an alternating magnetic field (AMF), obtaining Specific Absorption Rate (SAR) values of up to 51.87 ± 2.23 W/g for @Fe3O4-PEG6000. Additionally, the formed systems are susceptible to click chemistry, as was demonstrated in the case of the cannabidiol-propargyl derivative (CBD-Pro), which was synthesized and covalently attached to the azide functionalized surface of @Fe3O4-PEG400-N3. Prepared MNPs are highly dispersible in water, PBS, and citrate buffer, remaining in suspension for over 2 weeks, and non-toxic in the T84 human colon cancer cell line, Conclusions: indicating that they are ideal candidates for biomedical applications.

Carbon based nanocomposites, surface functionalization as a promising material for VOCs (volatile organic compounds) treatment.

Urban residential and industrial growth development affects sustainable and healthful indoor environments. Environmental issues are a global problem. The deterioration of indoor air quality has prompted the creation of several air cleansing techniques. This review explains how carbon-based materials have influenced the development of air purification systems using photocatalysis. These carbon-based materials offer unique properties and advantages in VOC removal processes. Biochar, produced from biomass pyrolysis, provides an environmentally sustainable solution with its porous structure and carbon-rich composition. Carbon quantum dots, with their quantum confinement effects and tunable surface properties, show promise in VOC sensing and removal applications. Polymers incorporating reduced graphene oxide demonstrate enhanced adsorption capabilities owing to the synergistic effects of graphene and polymer matrices. Activated carbon fibers, characterized by their high aspect ratio and interconnected porosity, provide efficient VOC removal with rapid kinetics. With their unique electronic and structural properties, graphitic carbon nitrides offer opportunities for photocatalytic degradation of VOCs under visible light. Catalysts integrated with MXene, a two-dimensional nanomaterial, exhibit enhanced catalytic activity for VOC oxidation reactions. Using various carbon-based materials in VOC removal showcases the versatility and effectiveness of carbon-based approaches in addressing environmental challenges associated with indoor air pollution. Metal-organic-framework materials are carbon-based compounds. It examines the correlation between VOC mineralization and specific characteristics of carbon materials, including surface area, adsorption capability, surface functional groups, and optoelectronic properties. Discussions include the basics of PCO, variables influencing how well catalysts degrade, and degradation mechanisms. It explores how technology will improve in the future to advance studies on healthy and sustainable indoor air quality.

A Calibration Strategy for Silicon Nanowire Field-Effect Transistor Biosensors and Its Application in Ultra-Sensitive, Label-Free Biosensing.

The silicon nanowire field-effect transistor (SiNW FET) has been developed for over two decades as an ultrasensitive, label-free biosensor for biodetection. However, inconsistencies in manufacturing and surface functionalization at the nanoscale have led to poor sensor-to-sensor consistency in performance. Despite extensive efforts to address this issue through process improvements and calibration methods, the outcomes have not been satisfactory. Herein, based on the strong correlation between the saturation response of SiNW FET biosensors and both their feature size and surface functionalization, we propose a calibration strategy that combines the sensing principles of SiNW FET with the Langmuir-Freundlich model. By normalizing the response of the SiNW FET biosensors (ΔI/I0) with their saturation response (ΔI/I0)max, this strategy fundamentally overcomes the issues mentioned above. It has enabled label-free detection of nucleic acids, proteins, and exosomes within 5 min, achieving detection limits as low as attomoles and demonstrating a significant reduction in the coefficient of variation. Notably, the nucleic acid test results exhibit a strong correlation with the ultraviolet-visible (UV-vis) spectrophotometer measurements, with a correlation coefficient reaching 0.933. The proposed saturation response calibration strategy exhibits good universality and practicability in biological detection applications, providing theoretical and experimental support for the transition of mass-manufactured nanosensors from theoretical research to practical application.

Advances in Light-Responsive Smart Multifunctional Nanofibers: Implications for Targeted Drug Delivery and Cancer Therapy.

Over the last decade, scientists have shifted their focus to the development of smart carriers for the delivery of chemotherapeutics in order to overcome the problems associated with traditional chemotherapy, such as poor aqueous solubility and bioavailability, low selectivity and targeting specificity, off-target drug side effects, and damage to surrounding healthy tissues. Nanofiber-based drug delivery systems have recently emerged as a promising drug delivery system in cancer therapy owing to their unique structural and functional properties, including tunable interconnected porosity, a high surface-to-volume ratio associated with high entrapment efficiency and drug loading capacity, and high mass transport properties, which allow for controlled and targeted drug delivery. In addition, they are biocompatible, biodegradable, and capable of surface functionalization, allowing for target-specific delivery and drug release. One of the most common fiber production methods is electrospinning, even though the relatively two-dimensional (2D) tightly packed fiber structures and low production rates have limited its performance. Forcespinning is an alternative spinning technology that generates high-throughput, continuous polymeric nanofibers with 3D structures. Unlike electrospinning, forcespinning generates fibers by centrifugal forces rather than electrostatic forces, resulting in significantly higher fiber production. The functionalization of nanocarriers on nanofibers can result in smart nanofibers with anticancer capabilities that can be activated by external stimuli, such as light. This review addresses current trends and potential applications of light-responsive and dual-stimuli-responsive electro- and forcespun smart nanofibers in cancer therapy, with a particular emphasis on functionalizing nanofiber surfaces and developing nano-in-nanofiber emerging delivery systems for dual-controlled drug release and high-precision tumor targeting. In addition, the progress and prospective diagnostic and therapeutic applications of light-responsive and dual-stimuli-responsive smart nanofibers are discussed in the context of combination cancer therapy.

Bioinspired Self-Growing Layered Hydrogel Enabled by Catechol Chemistry-Mediated Interfacial Catalytic System.

Tissue-inspired layered structural hydrogel has attracted increasing attention in artificial muscle, wound healing, wearable electronics, and soft robots. Despite numerous efforts being devoted to developing various layered hydrogels, the rapid and efficient preparation of layered hydrogels remains challenging. Herein, inspired by the self-growth concept of living organisms, an interfacial catalytic self-growth strategy based on catechol chemistry-mediated self-catalytic system of preparing layered hydrogels is demonstrated. Typically, the tannic acid-metal ion (e.g., TA-Fe3+) complex embedded in the hydrogel substrate would catalytically trigger rapid solid-liquid interfacial polymerization to grow the hydrogel layer without bulk solution polymerization. The self-growth process can be finely controlled by changing the growth time, the molar ratio of Fe3+/TA, and so on. The strategy is applicable to prepare various layered hydrogels as well as complex layered hydrogel patterns, allowing the customization of the physicochemical properties of the hydrogel. In addition, the self-adhesive layered hydrogel was prepared and can be utilized as a wearable strain sensor to monitor physiological activities and human motions. The demonstrated interfacial catalytic self-growth strategy will provide a route to design and fabricate layered hydrogel materials.

Functionalization of Polypropylene by TiO2 Photocatalytic Nanoparticles: On the Importance of the Surface Oxygen Plasma Treatment.

A new two-step method for developing a nanocomposite of polypropylene (PP) decorated with photocatalytically active TiO2 nanoparticles (nTiO2) is proposed. This method involves the low-temperature plasma functionalization of polypropylene followed by the ultrasound-assisted anchoring of nTiO2. The nanoparticles, polymeric substrate, and resultant nanocomposite were thoroughly characterized using nanoparticle tracking analysis (NTA), microscopic observations (SEM, TEM, and EDX), spectroscopic investigations (XPS and FTIR), thermogravimetric analysis (TG/DTA), and water contact angle (WCA) measurements. The photocatalytic activity of the nanocomposites was evaluated through the degradation of methyl orange. The individual TiO2 nanoparticles ranged from 2 to 6 nm in size. The oxygen plasma treatment of PP generated surface functional groups (mainly -OH and -C=O), transforming the surface from hydrophobic to hydrophilic, which facilitated the efficient deposition of nTiO2. Optimized plasma treatment and sonochemical deposition parameters resulted in an active photocatalytic nTiO2/PP system, degrading 80% of the methyl orange under UVA irradiation in 200 min. The proposed approach is considered versatile for the functionalization of polymeric materials with photoactive nanoparticles and, in a broader perspective, can be utilized for the fabrication of self-cleaning surfaces.

Graphene Oxide Surface Modification of Reverse Osmosis (RO) Membrane via Langmuir-Blodgett Technique: Balancing Performance and Antifouling Properties.

The reverse osmosis water treatment process is prone to fouling issues, prompting the exploration of various membrane modification techniques to address this challenge. The primary objective of this study was to develop a precise method for modifying the surface of reverse osmosis membranes to enhance their antifouling properties. The Langmuir-Blodgett technique was employed to transfer aminated graphene oxide films assembled at the air-liquid interface, under specific surface pressure conditions, to the polyamide surface with pre-activated carboxylic groups. The microstructure and distribution of graphene oxide along the modified membrane were characterized using SEM, AFM, and Raman mapping techniques. Modification carried out at the optimal surface pressure value improved the membrane hydrophilicity and reduced the surface roughness, thereby enhancing the antifouling properties against colloidal fouling. The flux recovery ratio after modification increased from 65% to 87%, maintaining high permeability. The modified membranes exhibited superior performance compared to the unmodified membranes during long-term fouling tests. This membrane modification technique can be easily scaled using the roll-to-roll approach and requires minimal consumption of the modifier used.

Recent Advances in Functionalized Biomass-Derived Porous Carbons and their Composites for Hybrid Ion Capacitors.

Hybrid ion capacitors (HICs) have aroused extreme interest due to their combined characteristics of energy and power densities. The performance of HICs lies hidden in the electrode materials used for the construction of battery and supercapacitor components. The hunt is always on to locate the best material in terms of cost-effectiveness and overall optimized performance characteristics. Functionalized biomass-derived porous carbons (FBPCs) possess exquisite features including easy synthesis, wide availability, high surface area, large pore volume, tunable pore size, surface functional groups, a wide range of morphologies, and high thermal and chemical stability. FBPCs have found immense use as cathode, anode and dual electrode materials for HICs in the recent literature. The current review is designed around two main concepts which include the synthesis and properties of FBPCs followed by their utilization in various types of HICs. Among monovalent HICs, lithium, sodium, and potassium, are given comprehensive attention, whereas zinc is the only multivalent HIC that is focused upon due to corresponding literature availability. Special attention is also provided to the critical factors that govern the performance of HICs. The review concludes by providing feasible directions for future research in various aspects of FBPCs and their utilization in HICs.

Extracellular vesicle surface display enhances the therapeutic efficacy and safety profile of cancer immunotherapy.

Immunotherapy has emerged as a mainstay in cancer therapy, yet its efficacy is constrained by the risk of immune-related adverse events. In this study, we present a nanoparticle-based delivery system that enhances the therapeutic efficacy of immunomodulatory ligands while concurrently limiting systemic toxicity. We demonstrate that extracellular vesicles (EVs), lipid bilayer enclosed particles released by cells, can be efficiently engineered via inverse electron demand Diels-Alder (iEDDA)-mediated conjugation to display multiple immunomodulatory ligands on their surface. Display of immunomodulatory ligands on the EV surface conferred substantial enhancements in signaling efficacy, particularly for tumor necrosis factor receptor superfamily (TNFRSF) agonists, where the EV surface display served as an alternative FcγR-independent approach to induce ligand multimerization and efficient receptor crosslinking. EVs displaying a complementary combination of immunotherapeutic ligands were able to shift the tumor immune milieu toward an anti-tumorigenic phenotype and significantly suppress tumor burden and increase survival in multiple models of metastatic cancer to a greater extent than an equivalent dose of free ligands. In summary, we present an EV-based delivery platform for cancer immunotherapeutic ligands that facilitates superior anti-tumor responses at significantly lower doses with fewer side effects than is possible with conventional delivery approaches.

Advances of Fluorescent Nanodiamond Platforms for Intracellular and On-Chip Biosensing.

Intracellular and extracellular sensing of physical and chemical variables is important for disease diagnosis and the understanding of cellular biology. Optical sensing utilizing fluorescent nanodiamonds (FNDs) is promising for probing intracellular and extracellular variables owing to their biocompatibility, photostability, and sensitivity to physicochemical quantities. Based on the potential of FNDs, we outlined the optical properties, biocompatibility, surface chemistry of FNDs and their applications in intracellular biosensing. This review also introduces biosensing platforms that combine FNDs and lab-on-a-chip approaches to control the extracellular environment and improve sample/reagent handling and sensing performance.