Nanomaterials for Molecular Detection and Analysis of Extracellular Vesicles.

Extracellular vesicles (EVs) have emerged as a novel resource of biomarkers for cancer and certain other diseases. Probing EVs in body fluids has become of major interest in the past decade in the development of a new-generation liquid biopsy for cancer diagnosis and monitoring. However, sensitive and specific molecular detection and analysis are challenging, due to the small size of EVs, low amount of antigens on individual EVs, and the complex biofluid matrix. Nanomaterials have been widely used in the technological development of protein and nucleic acid-based EV detection and analysis, owing to the unique structure and functional properties of materials at the nanometer scale. In this review, we summarize various nanomaterial-based analytical technologies for molecular EV detection and analysis. We discuss these technologies based on the major types of nanomaterials, including plasmonic, fluorescent, magnetic, organic, carbon-based, and certain other nanostructures. For each type of nanomaterial, functional properties are briefly described, followed by the applications of the nanomaterials for EV biomarker detection, profiling, and analysis in terms of detection mechanisms.

Dual Imaging Single Vesicle Surface Protein Profiling and Early Cancer Detection.

Single vesicle molecular profiling has the potential to transform cancer detection and monitoring by precisely probing cancer-associated extracellular vesicles (EVs) in the presence of normal EVs in body fluids, but it is challenging due to the small EV size, low abundance of antigens on individual vesicles, and a complex biological matrix. Here, we report a facile dual imaging single vesicle technology (DISVT) for surface protein profiling of individual EVs and quantification of target-specific EV subtypes based on direct molecular capture of EVs from diluted biofluids, dual EV-protein fluorescence-light scattering imaging, and fast image analysis using Bash scripts, Python, and ImageJ. Plasmonic gold nanoparticles (AuNPs) were used to label and detect targeted surface protein markers on individual EVs with dark-field light scattering imaging at the single particle level. Monte Carlo calculations estimated that the AuNPs could detect EVs down to 40 nm in diameter. Using the DISVT, we profiled surface protein markers of interest across individual EVs derived from several breast cancer cell lines, which reflected the parental cells. Studies with plasma EVs from healthy donors and breast cancer patients revealed that the DISVT, but not the traditional bulk enzyme-linked immunosorbent assay, detected human epidermal growth factor receptor 2 (HER2)-positive breast cancer at an early stage. The DISVT also precisely differentiated HER2-positive breast cancer from HER2-negative breast cancer. We additionally showed that the amount of tumor-associated EVs was tripled in locally advanced patients compared to that in early-stage patients. These studies suggest that single EV surface protein profiling with DISVT can provide a facile and high-sensitivity method for early cancer detection and quantitative monitoring.

Gold Nanorod-Assisted Photothermal Therapy and Improvement Strategies.

Noble metal nanoparticles have been sought after in cancer nanomedicine during the past two decades, owing to the unique localized surface plasmon resonance that induces strong absorption and scattering properties of the nanoparticles. A popular application of noble metal nanoparticles is photothermal therapy, which destroys cancer cells by heat generated by laser irradiation of the nanoparticles. Gold nanorods have stood out as one of the major types of noble metal nanoparticles for photothermal therapy due to the facile tuning of their optical properties in the tissue penetrative near infrared region, strong photothermal conversion efficiency, and long blood circulation half-life after surface modification with stealthy polymers. In this review, we will summarize the optical properties of gold nanorods and their applications in photothermal therapy. We will also discuss the recent strategies to improve gold nanorod-assisted photothermal therapy through combination with chemotherapy and photodynamic therapy.