Nano Pom-poms Prepared Highly Specific Extracellular Vesicles Expand the Detectable Cancer Biomarkers

Abstract

Extracellular vesicles (EVs), particularly exosomes, are emerging biomarker sources. However, due to heterogeneous populations secreted from diverse cell types, mapping EV multi-omic molecular information specifically to their pathogenesis origin for cancer biomarker identification is still extraordinary challenging. Herein, we introduced a novel 3D-structured nanographene immunomagnetic particles (NanoPoms) with unique flower pom-poms morphology and photo-click chemistry for specific marker-defined capture and release of intact small EVs. This specific EV isolation approach leads to the expanded identification of targetable cancer biomarkers with enhanced specificity and sensitivity, as demonstrated by multi-omic EV analysis of bladder cancer patient tissue fluids using the next generation sequencing of somatic DNA mutations, miRNAs, and the global proteome. The NanoPoms prepared sEVs also exhibit distinctive in vivo biodistribution patterns, highlighting the highly viable and integral quality. The developed method is simple and straightforward, and is applicable to nearly all types of biological fluids and amenable for scale up and high-throughput EV isolation.

Development of surface engineered antigenic exosomes as vaccines for respiratory syncytial virus

“…The unique nano-morphology of these ExoRelease particles was shown in Fig. 1B, which enables more efficient capture of exosomes than conventional beads due to much larger surface area and comparable nano-scale cavities 19 . After capture, the uniform, dense, and nano-sized exosomes were shown covering the entire surface of ExoRelease particles (Fig.…”

Isolation of sensory hair cell specific exosomes in human perilymph

“…The developed immunomagnetic nano pom-poms are uniquely position for isolating exosomes from precious volume of human perilymph fluids, owning to the highly specific exosome capture-release process and magnetic field aggregation for exosome enrichment which is particularly essential for handling ultra-low sample volume. In this work, we demonstrated first time to be able to isolate perilymph exosomes and probe the specific hair cell markers myosin VIIa from isolated perilymph exosomes, which is much more sensitive than ultracentrifugation exosome isolation approaches [ 27 ]. The distribution of cytosolic and transmembrane proteins that are enriched in the in the inner ear and their localization within perilymph exosomes will need to be evaluated to expand potential applications of this technology.…”

“…The developed immunomagnetic nano pom-poms allow the exosome capture via a specific antibody from ultra-low sample volume. Under magnetic field aggregation, the captured exosomes can be enriched, and on-demand released through the conjugated photo-click chemistry on the nano pom-poms surface, in turn, harvesting intact exosomes for enhancing the exosomal marker detection specificity and sensitivity [ 26 , 27 ]. The isolated exosomes exhibit specific expression of protein myosin VIIa (MYO7A) in relation to the status of hearing loss.…”

Isolation of sensory hair cell specific exosomes in human perilymph

“…The developed immunomagnetic nano pom-poms are uniquely position for isolating exosomes from precious volume of human perilymph fluids, owning to the highly specific exosome capturerelease process and magnetic field aggregation for exosome enrichment which is particularly essential for handling ultra-low sample volume. In this work, we demonstrated first time to be able to isolate perilymph exosomes and probe the specific myosin VIIa hair cell markers from isolated perilymph exosomes, which is much more sensitive than ultracentrifugation exosome isolation approach(N. He et al, 2021).…”

“…The developed immunomagnetic nano pom-poms allow the exosome capture via specific antibody from ultra-low sample volume. Under magnetic field aggregation, the captured exosomes can be enriched, and on-demand released through the conjugated photo-click chemistry on the nano pom-poms surface, in turn, harvesting intact exosomes for enhancing the exosomal marker detection specificity and sensitivity(N. He et al, 2021;Zhao, McGill, Gamero-Kubota, & He, 2019) . The isolated exosomes exhibit specific expression of protein myosin VII in relation to the status of hearing loss.…”