The concept of liquid biopsy has emerged as a novel approach for cancer screening, which is based on the analysis of circulating cancer biomarkers in body fluids. Among the various circulating cancer biomarkers, including Food and Drug Administration (FDA)-approved circulating tumor cells (CTC) and circulating tumor DNA (ctDNA), exosomes have attracted tremendous attention due to their ability to diagnose cancer in its early stages with high efficiency. Recently, surface-enhanced Raman spectroscopy (SERS) has been applied for the detection of cancer exosomes due to its high sensitivity, specificity, and multiplexing capability. In this article, we review recent progress in the development of SERS-based technologies for in vitro identification of circulating cancer exosomes. The accent is made on the detection strategies and interpretation of the SERS data. The problems of detecting cancer-derived exosomes from patient samples and future perspectives of SERS-based diagnostics are also discussed.

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We present a targeted drug delivery system for therapy and diagnostics that is based on a combination of contrasting, cytotoxic, and cancer-cell-targeting properties of multifunctional carriers. The system uses multilayered polymer microcapsules loaded with magnetite and doxorubicin. Loading of magnetite nanoparticles into the polymer shell by freezing-induced loading (FIL) allowed the loading efficiency to be increased 5-fold, compared with the widely used layer-by-layer (LBL) assembly. FIL also improved the photoacoustic signal and particle mobility in a magnetic field gradient, a result unachievable by the LBL alone. For targeted delivery of the carriers to cancer cells, the carrier surface was modified with a designed ankyrin repeat protein (DARPin) directed toward the epithelial cell adhesion molecule (EpCAM). Flow cytometry measurements showed that the DARPin-coated capsules specifically interacted with the surface of EpCAM-overexpressing human cancer cells such as MCF7. In vivo and ex vivo biodistribution studies in FvB mice showed that the carrier surface modification with DARPin changed the biodistribution of the capsules toward epithelial cells. In particular, the capsules accumulated substantially in the lungsa result that can be effectively used in targeted lung cancer therapy. The results of this work may aid in the further development of the “magic bullet” concept and may bring the quality of personalized medicine to another level.

Super-resolution optoacoustic imaging of microvascular structures deep in mammalian tissues has so far been impeded by strong absorption from densely-packed red blood cells. Here we devised 5 µm biocompatible dichloromethane-based microdroplets exhibiting several orders of magnitude higher optical absorption than red blood cells at near-infrared wavelengths, thus enabling single-particle detection in vivo. We demonstrate non-invasive three-dimensional microangiography of the mouse brain beyond the acoustic diffraction limit (<20 µm resolution). Blood flow velocity quantification in microvascular networks and light fluence mapping was also accomplished. In mice affected by acute ischemic stroke, the multi-parametric multi-scale observations enabled by super-resolution and spectroscopic optoacoustic imaging revealed significant differences in microvascular density, flow and oxygen saturation in ipsi- and contra-lateral brain hemispheres. Given the sensitivity of optoacoustics to functional, metabolic and molecular events in living tissues, the new approach paves the way for non-invasive microscopic observations with unrivaled resolution, contrast and speed.