Abstract
A liquid biopsy based on circulating small extracellular vesicles (SEVs) has not yet been used in routine clinical practice due to the lack of reliable analytic technologies. Recent studies have demonstrated the great diagnostic potential of nanozyme-based systems for the detection of SEV markers. Here, we hypothesize that CD30-positive Hodgkin and Reed–Sternberg (HRS) cells secrete CD30 + SEVs; therefore, the relative amount of circulating CD30 + SEVs might reflect classical forms of Hodgkin lymphoma (cHL) activity and can be measured by using a nanozyme-based technique. A AuNP aptasensor analytics system was created using aurum nanoparticles (AuNPs) with peroxidase activity. Sensing was mediated by competing properties of DNA aptamers to attach onto surface of AuNPs inhibiting their enzymatic activity and to bind specific markers on SEVs surface. An enzymatic activity of AuNPs was evaluated through the color reaction. The study included characterization of the components of the analytic system and its functionality using transmission and scanning electron microscopy, nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), and spectrophotometry. AuNP aptasensor analytics were optimized to quantify plasma CD30 + SEVs. The developed method allowed us to differentiate healthy donors and cHL patients. The results of the CD30 + SEV quantification in the plasma of cHL patients were compared with the results of disease activity assessment by positron emission tomography/computed tomography (PET-CT) scanning, revealing a strong positive correlation. Moreover, two cycles of chemotherapy resulted in a statistically significant decrease in CD30 + SEVs in the plasma of cHL patients. The proposed AuNP aptasensor system presents a promising new approach for monitoring cHL patients and can be modified for the diagnostic testing of other diseases.
Highlights
The classical form of Hodgkin lymphoma is a lymphoid malignancy with malignant cells (Hodgkin and Reed–Sternberg (HRS) cells) representing only a small percentage of a tumor’s volume; the tumor is mostly composed of non-neoplastic infiltrating cells
If the development of classical form of Hodgkin lymphoma (cHL) is associated with the appearance of HRS-cell-derived Small extracellular vesicles (SEVs) in circulation, the vesicles positive for CD30 and/or other cHL-specific molecules might serve as disease-indicative markers
These results indicated a collapse of the analytic system, when single-stranded DNA (ssDNA) caused a crucial aggregation of aurum nanoparticles (AuNPs)
Summary
The classical form of Hodgkin lymphoma (cHL) is a lymphoid malignancy with malignant cells (Hodgkin and Reed–Sternberg (HRS) cells) representing only a small percentage of a tumor’s volume; the tumor is mostly composed of non-neoplastic infiltrating cells. In contrast to the above-mentioned reports describing aptasensors for SEV detection, Wang et al demonstrated that ssDNA was adsorbed on the surface of AuNPs via nonspecific electrostatic interactions and thereby blocked the peroxidase activity of nanoparticles [14]. The goal of the present study was to explore the sensitivity of a AuNP aptasensor for the quantification of CD30 + SEVs in the plasma of cHL patients and to test the diseaseindicative potential of such quantification. With this purpose, we evaluated the suppressing effects of ssDNA aptamer adsorption on the peroxidase activity of AuNPs and created a. The proposed AuNP aptasensor presents a promising technology that can be further optimized and evaluated in clinical settings as a new approach for cHL monitoring and the early detection of disease recurrence
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