Application of Dynamic and Static Light Scattering for Size and Shape Characterization of Small Extracellular Nanoparticles in Plasma and Ascites of Ovarian Cancer Patients.

Ksenija Kogej,Katarina Černe,Darja Božič,Borut Kobal,Maruša Herzog

doi:10.3390/ijms222312946

Abstract

In parallel to medical treatment of ovarian cancer, methods for the early detection of cancer tumors are being sought. In this contribution, the use of non-invasive static (SLS) and dynamic light scattering (DLS) for the characterization of extracellular nanoparticles (ENPs) in body fluids of advanced serous ovarian cancer (OC) and benign gynecological pathology (BP) patients is demonstrated and critically evaluated. Samples of plasma and ascites (OC patients) or plasma, peritoneal fluid, and peritoneal washing (BP patients) were analyzed. The hydrodynamic radius (Rh) and the radius of gyration (Rg) of ENPs were calculated from the angular dependency of LS intensity for two ENP subpopulations. Rh and Rg of the predominant ENP population of OC patients were in the range 20–30 nm (diameter 40–60 nm). In thawed samples, larger particles (Rh mostly above 100 nm) were detected as well. The shape parameter ρ of both particle populations was around 1, which is typical for spherical particles with mass concentrated on the rim, as in vesicles. The Rh and Rg of ENPs in BP patients were larger than in OC patients, with ρ ≈ 1.1–2, implying a more elongated/distorted shape. These results show that SLS and DLS are promising methods for the analysis of morphological features of ENPs and have the potential to discriminate between OC and BP patients. However, further development of the methodology is required.

Highlights

Ovarian cancer (OC) is a highly aggressive type of tumor
We start with presenting dynamic light scattering (DLS) measurements at a single scattering angle θ (=90◦), which is the approach usually followed in DLS studies of extracellular nanoparticles (ENPs) and exosomes in the past [59,60,61]
Note that filtering is necessary in Light scattering (LS) experiments, especially in the case of aqueous systems, which have a large tendency to bind dust particles as these may have a strong effect on the collected LS data

Summary

Introduction

Ovarian cancer (OC) is a highly aggressive type of tumor. Recurrence is frequently accompanied by the development of carcinomatosis, which may not be amenable to surgery [7], and is almost always fatal. These facts clearly indicate the need for early diagnosis of the disease, which, requires new analytical approaches. In this context, extracellular vesicles (EVs), including the recently frequently investigated exosomes, are gaining considerable research interest due to their diagnostic and therapeutic potential, in particular in cancer therapy [8,9,10,11,12]. The release of EVs into human blood and other body fluids (e.g., ascites, urine, and saliva) may be enhanced several times under pathological conditions [13,14,15,16,17]

Methods

Results

Discussion

Conclusion