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arXiv · 2312.03554

Size stability and self-agglomeration of erythrocyte-derived membrane nanovesicles versus physiological extracellular vesicles

Maryam Sanaee·K. Göran Ronquist·Jane M. Morrell·Muhammet S. Toprak·Katia Gallo
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Abstract

Extracellular vesicles (EVs) and plasma membrane-derived exosome-mimetic nanovesicles demonstrate significant potential for drug delivery. Latter synthetic provides higher throughput over physiological EVs. However they face size-stability and self-agglomeration challenges in physiological solutions to be properly characterized and addressed. Here we demonstrate a fast and high-throughput nanovesicle screening methodology relying on dynamic light scattering (DLS) complemented by atomic force microscopy (AFM) measurements, suitable for the evaluation of hydrodynamic size instabilities and aggregation effects in nanovesicle solutions under varying experimental conditions and apply it to the analysis of bio-engineered nanovesicles derived from erythrocytes as well as physiological extracellular vesicles isolated from animal seminal plasma. The synthetic vesicles exhibit a significantly higher degree of agglomeration, with only 8 % of them falling within the typical extracellular vesicle size range (30-200 nm) in their original preparation conditions. Concurrent zeta potential measurements performed on both physiological and synthetic nanovesicles yielded values in the range of -17 to -22 mV, with no apparent correlation to their agglomeration tendencies. However, mild sonication and dilution were found to be effective means to restore the portion of EVs-like nanovesicles in synthetic preparations to values of 54% and 63%, respectively, The results illustrate the capability of this DLS-AFM-based analytical method for real-time, high-throughput and quantitative assessments of agglomeration effects and size instabilities in bioengineered nanovesicle solutions, providing a powerful and easy-to-use tool to gain insights to overcome such deleterious effects and leverage the full potential of this promising biocompatible drug-delivery carriers for a broad range of pharmaceutical applications.

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Maryam Sanaee, K. Göran Ronquist, Jane M. Morrell, Muhammet S. Toprak, Katia Gallo. 2023-12-06. Size stability and self-agglomeration of erythrocyte-derived membrane nanovesicles versus physiological extracellular vesicles. https://arxiv.org/abs/2312.03554

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