Efficient isolation and analysis of exosomal biomarkers hold transformative potential in biomedical applications. However, current methods are prone to contamination and require costly consumables, expensive equipment, and skilled personnel. Here, we introduce an innovative spaceship-like disc that allows Acoustic Separation and Concentration of Exosomes and Nucleotide Detection: ASCENDx. We created ASCENDx to use acoustically driven disc rotation on a spinning droplet to generate swift separation and concentration of exosomes from patient plasma samples. Integrated plasmonic nanostars on the ASCENDx disc enable label-free detection of enriched exosomes via surface-enhanced Raman scattering. Direct detection of circulating exosomal microRNA biomarkers from patient plasma samples by the ASCENDx platform facilitated a diagnostic assay for colorectal cancer with 95.8% sensitivity and 100% specificity. ASCENDx overcomes existing limitations in exosome-based molecular diagnostics and holds a powerful position for future biomedical research, precision medicine, and point-of-care medical diagnostics.

Acoustically probing biological tissues with light or sound, photoacoustic and ultrasound imaging can provide anatomical, functional, and/or molecular information at depths far beyond the optical diffusion limit. However, most photoacoustic and ultrasound imaging systems rely on linear-array transducers with elevational focusing and are limited to two-dimensional imaging with anisotropic resolutions. Here, we present three-dimensional diffractive acoustic tomography (3D-DAT), which uses an off-the-shelf linear-array transducer with single-slit acoustic diffraction. Without jeopardizing its accessibility by general users, 3D-DAT has achieved simultaneous 3D photoacoustic and ultrasound imaging with optimal imaging performance in deep tissues, providing near-isotropic resolutions, high imaging speed, and a large field-of-view, as well as enhanced quantitative accuracy and detection sensitivity. Moreover, powered by the fast focal line volumetric reconstruction, 3D-DAT has achieved 50-fold faster reconstruction times than traditional photoacoustic imaging reconstruction. Using 3D-DAT on small animal models, we mapped the distribution of the biliverdin-binding serpin complex in glassfrogs, tracked gold nanoparticle accumulation in a mouse tumor model, imaged genetically-encoded photoswitchable tumors, and investigated polyfluoroalkyl substances exposure on developing embryos. With its enhanced imaging performance and high accessibility, 3D-DAT may find broad applications in fundamental life sciences and biomedical research.

Nanoparticle-mediated photothermal therapy (PTT) is a promising strategy for cancer treatment; however, nanoparticle instability and lack of precise imaging tools for real-time temperature monitoring during therapy and nanoparticle tracking have hindered investigations in animal models. To address these critical issues, we present a theranostic platform that seamlessly integrates armored core–gold nanostar (AC-GNS)–mediated PTT with full-view photoacoustic computed tomography (PACT), enabling nanoparticle tracking and real-time imaging-guided PTT in deep tissues. The AC-GNS platform delivered exceptional photostability and thermal resilience beyond those of conventional nanoparticles while serving as a high-performance contrast agent for PACT and a photothermal transducer for PTT. Integrating AC-GNS–mediated PTT with noninvasive PACT enabled whole-body nanoparticle tracking, PTT treatment monitoring via thermal imaging, and thermal dose determination, culminating in a 100% survival rate in a murine bladder cancer model without long-term treatment-related toxicity. This theranostic platform lays the foundation for broader research applications and provides opportunities for advancing solid tumor treatment and response assessment research.

Background: Matrix-bound nanovesicles (MBV) are extracellular vesicles (EVs) that are embedded within the extracellular matrix (ECM), and they have shown immunomodulatory effects in various cell types. The THP-1 cell line is often used to study monocyte and macrophage functions due to its easy culture potential and relatively simple conditioning into different macrophage phenotypes, but the optimal culturing conditions that allow MBV immunomodulation have not been established. Methods: In this study, we evaluated different culturing and differentiation conditions of THP-1 cells in which MBVs showed immunomodulatory effects. We also studied the effect of MBVs on relevant inflammation pathways (NF-κB and ERK 1/2). Results: Quantification of inflammatory cytokine IL-6 indicated modulation effects by MBVs in the majority of the conditions, but TNF-α showed very limited modulation. ERK1/p44 phosphorylation was significantly increased in MBV groups, but NF-κB protein p65 expression was unaffected. When compared to serum EVs, vesicle uptake by THP-1 cells remained low after 24 h. Multispectral flow cytometry analysis of THP-1 cells exposed to MBV and serum EVs showed internalization of lipids, proteins and RNA within the cells in higher cell proportions, but colocalization of the different vesicle components was not observed. Conclusions: Overall, this study provided insights into MBV immunomodulatory effects on THP-1 cells and compared the effects of MBV and serum EVs. Slight differences in modulation were observed between both EV sources, pointing to cargo differences that need further investigation.