Nano–Bio Interactions of Extracellular Vesicles with Gold Nanoislands for Early Cancer Diagnosis

Abstract

<jats:p>Extracellular vesicles or exosomes are membrane encapsulated biological nanometric particles secreted virtually by all types of cells throughout the animal kingdom. They carry a cargo of active molecules to proximal and distal cells of the body as mechanism of physiological communication, to maintain natural homeostasis as well as pathological responses. Exosomes carry a tremendous potential for liquid biopsy and therapeutic applications. Thus, there is a global demand for simple and robust exosome isolation methods amenable to point-of-care diagnosis and quality control of therapeutic exosome manufacturing. This can be achieved by molecular profiling of the exosomes for use with specific sets of molecular-markers for diagnosis and quality control. Liquid biopsy is undoubtedly the most promising diagnosis process to advance “personalized medicine.” Currently, liquid biopsy is based on circulating cancer cells, cell free-DNA, or exosomes. Exosomes potentially provide promise for early-stage diagnostic possibility; in order to facilitate superior diagnosis and isolation of exosomes, a novel platform is developed to detect and capture them, based on localized surface plasmon resonance (LSPR) of gold nanoislands, through strong affinity between exosomes and peptide called Venceremin or Vn96. Physical modeling, based on the characteristics of the gold nanoislands and the bioentities involved in the sensing, is also developed to determine the detection capability of the platform, which is optimized experimentally at each stage. Preliminary results and modeling present a relationship between the plasmonic shift and the concentration of exosomes and, essentially, indicate possibilities for label-free early diagnosis.</jats:p>

Gold Nano-Island Platforms for Localized Surface Plasmon Resonance Sensing: A Short Review

“…Our group principally investigated the analytical performance of nano-islands, prepared by the dewetting of gold nanoparticle films [ 41 , 42 , 43 , 44 , 45 , 46 ]. The principal motivation for this work was the need for a simple and rapid method of detection of growth hormone levels in milk and milk products.…”

“… Schematic of the deposition of AuNP (Nanoparticle) multilayers by a thermal convection method (modified from Bathini [ 42 ]. …”

Noble Metal-Assisted Surface Plasmon Resonance Immunosensors

“…This sensor could detect exosome concentrations ranging from 0.194 to 100 µg/mL. Bathini et al detailed an Au nanoisland-assisted exosome detection platform with a streptavidin-biotin-polyethylene glycol (PEG)-venceremin (Vn96) complex [89]. Vn96, is a synthetic peptide, having a high affinity for heat shock proteins (HSPs) on the surface of exosomes.…”

When Less Is More: Specific Capture and Analysis of Tumor Exosomes in Plasma Increases the Sensitivity of Liquid Biopsy for Comprehensive Detection of Multiple Androgen Receptor Phenotypes in Advanced Prostate Cancer Patients

“…Although some HSPs are considered common exosome markers, their expression is highly increased on the surface of tumor cells and there-released vesicles, with respect to vesicles coming from non-tumor cells. Thus, Vn96 provides a stronger affinity capture of HSP-overexpressed exosomes from a given body fluid, which is claimed to provide superior diagnostic value for cancer diagnoses [13]. This step of incubation with the ME TM kit, according to the manifacturer's instructions, was followed by Trizol-based RNA purification; (3) moreover, the exoRNeasy serum/plasma kit (Qiagen, Venlo, The Netherlands), a more generic extraction protocol that takes advantage of membrane-affinity columns (exoEasy columns) to bind exosomes and other EVs, was used.…”