Buoyant Metal-Organic Framework Corona-Driven Fast Isolation and Ultrasensitive Profiling of Circulating Extracellular Vesicles.

Accurately assaying tumor-derived circulating extracellular vesicles (EVs) is fundamental in noninvasive cancer diagnosis and therapeutic monitoring but limited by challenges in efficient EV isolation and profiling. Here, we report a bioinspired buoyancy-driven metal-organic framework (MOF) corona that leverages on-bubble coordination and dual-encoded surface-enhanced Raman scattering (SERS) nanotags to streamline rapid isolation and ultrasensitive profiling of plasma EVs in a single assay for cancer diagnostics. This integrated bubble-MOF-SERS EV assay (IBMsv) allows barnacle-like high-density adhesion of MOFs on a self-floating bubble surface to enable fast isolation (2 min, near 90% capture efficiency) of tumor EVs via enhanced EV-MOF binding. Also, IBMsv harnesses four-plexed SERS nanotags to profile the captured EV surface protein markers at a single-particle level. Such a sensitive assay allows multiplexed profiling of EVs across five cancer types, revealing heterogeneous EV surface expression patterns. Furthermore, the IBMsv assay enables cancer diagnosis in a pilot clinical cohort (n = 55) with accuracies >95%, improves discrimination between cancer and noncancer patients via an algorithm, and monitors the surgical treatment response from hepatocellular carcinoma patients. This assay provides a fast, sensitive, streamlined, multiplexed, and portable blood test tool to enable cancer diagnosis and response monitoring in clinical settings.

Bioorthogonal Microbubbles with Antifouling Nanofilm for Instant and Suspended Enrichment of Circulating Tumor Cells.

Integrating clinical rare cell enrichment, culture, and single-cell phenotypic profiling is currently hampered by the lack of competent technologies, which typically suffer from weak cell-interface collision affinity, strong nonspecific adsorption, and the potential uptake. Here, we report cells-on-a-bubble, a bioinspired, self-powered bioorthogonal microbubble (click bubble) that leverages a clickable antifouling nanointerface and a DNA-assembled sucker-like polyvalent cell surface, to enable instant and suspended isolation of circulating tumor cells (CTCs) within minutes. Using this biomimetic engineering strategy, click bubbles achieve a capture efficiency of up to 98%, improved by 20% at 15 times faster over their monovalent counterparts. Further, the buoyancy-activated bubble facilitates self-separation, 3D suspension culture, and in situ phenotyping of the captured single cancer cells. By using a multiantibody design, this fast, affordable micromotor-like click bubble enables suspended enrichment of CTCs in a cohort (n = 42) across three cancer types and treatment response evaluation, signifying its great potential to enable single-cell analysis and 3D organoid culture.

Simultaneous detection of cancerous exosomal miRNA-21 and PD-L1 with a sensitive dual-cycling nanoprobe.

Simultaneous detection of specific exosomal surface proteins and inner microRNAs are hampered by their heterogeneity, low abundance and spatial segregation in nanovesicles. Here, we design a dual-cycling nanoprobe (DCNP) to enable single-step simultaneous quantitation of cancerous exosomal surface programmed death-ligand 1 (PD-L1) (ExoPD-L1) and miRNA-21 (ExomiR-21) directly in exosome lysates, without resorting to either RNA extraction or time-consuming transmembrane penetration. In this design, DNA molecular machine-based dual-recognition probes co-assemble onto gold nanoparticle surface for engineering 'silent' DCNPs, which enable signal-amplified synchronous response to dual-targets as activated by ExomiR-21 and ExoPD-L1 within 20 min. Benefiting from cycling amplification of the molecular machine, DCNPs sensor achieves detection limits of tumor exosomes, ExoPD-L1 and ExomiR-21 down to 10 particles/µL, 0.17 pg/mL and 66 fM, respectively. Such a sensitive dual-response strategy allows simultaneous tracking the dynamic changes of ExoPD-L1 and ExomiR-21 expression regulated by signaling molecules or therapeutics. This approach further detects circulating ExoPD-L1 and ExomiR-21 in human plasma to differentiate breast cancer patients from healthy individuals with high accuracy, showing great potential of DCNPs for simultaneous profiling exosomal surface and inside biomarkers, and for clinical precision diagnosis.

Early Diastolic Longitudinal Strain Rate at MRI and Outcomes in Heart Failure with Preserved Ejection Fraction.

Background Assessment of subclinical myocardial dysfunction by using feature tracking has shown promise in prognosis evaluation of heart failure with preserved ejection fraction (HFpEF). Global early diastolic longitudinal strain rate (eGLSR) can identify earlier diastolic dysfunction; however, limited data are available on its prognostic value in HFpEF. Purpose To evaluate the association between left ventricular (LV) eGLSR and primary composite outcomes (all-cause death or heart failure hospitalization) in patients with HFpEF. Materials and Methods In this retrospective study, consecutive patients with HFpEF (included from January 2010 to March 2013) underwent cardiovascular MRI. The correlation between eGLSR and variables was assessed by using linear regression. The association between eGLSR (obtained with use of feature tracking) and outcomes was analyzed by using Cox proportional regression. Results A total of 186 patients with HFpEF (mean age ± standard deviation, 59 years ± 12; 77 women) were included. The eGLSR was weakly correlated with LV end-diastole volume index (Pearson correlation coefficient [r] = -0.35; P < .001), heart rate (r = 0.35; P < .001), and LV ejection fraction (r = 0.30; P < .001) and moderately correlated with LV end-systole volume index (r = -0.41; P < .001). At a median follow-up of 9.2 years (interquartile range, 8.7-10.0 years), 72 patients experienced primary composite outcomes. Impaired eGLSR, defined as an eGLSR of less than 0.57 per second, was associated with a greater rate of heart failure hospitalization or all-cause death (hazard ratio, 2.0 [95% CI: 1.1, 3.7]; P = .02) after adjusting for multiple clinical and imaging-based variables. Conclusion Left ventricular global early diastolic longitudinal strain rate obtained from cardiovascular MRI feature tracking was independently associated with adverse outcomes in patients with heart failure with preserved ejection fraction. © RSNA, 2021 Online supplemental material is available for this article. An earlier incorrect version appeared online. This article was corrected on October 22, 2021.