Abstract

To understand the factors that control the formation of the biomolecular corona, a systematic study of the adsorption of several miRNAs shown to be important in prostate cancer on amine-functionalized mesoporous silica nanoparticles (MSN-NH2) has been performed. Process parameters including miRNA type, nanoparticle concentration, incubation temperature and incubation time were investigated, as well as the potential competition for adsorption between different miRNA molecules. The influence of proteins and particle PEGylation on miRNA adsorption were also explored. We found that low particle concentrations and physiological temperature both led to increased miRNA adsorption. Adsorption of miRNA was also higher when proteins were present in the same solution; reducing or preventing protein adsorption by PEGylating the MSNs hindered adsorption. Finally, the amount of miRNA adsorbed from human serum by MSN-NH2 was compared to a commercial miRNA purification kit (TaqMan®, Life Technologies, Carlsbad, CA, USA). MSN-NH2 adsorbed six times as much miRNA as the commercial kit, demonstrating higher sensitivity to subtle up- and downregulation of circulating miRNA in the blood of patients.

Highlights

  • With goaltoof eventuallythe developing a diagnosticbetween test based on biomolecules cirIn thisthe sense, investigate potential competition different miRNA molculating in the blood and accessible for simple analysis, the miRNAs selected have been ecules for adsorption into the pores of mesoporous silica nanoparticles (MSNs)-NH2, we studied the miRNA adsorption proshown to be either downregulated in the of prostate cancer patients

  • In the factors that control the formation of the biomolecular corona on mesoporous silica deed, MSN-NH

  • Adsorption was optimum with silica nanoparticles were able to isolate about 70% of the miRNA spiked inlow the serum concentrations of MSN-NH

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Summary

Introduction

The interaction of molecules from biological samples (e.g., from blood) with nanoparticles promotes a series of processes leading to the formation of the so-called “biomolecular corona” [1,2,3,4,5,6,7], a multilayered mass of biomolecules including proteins, RNA, lipids, carbohydrates that adsorbs from solution onto the surface of the nanoparticles. A few years ago, the concept of using the “personalized biomolecular corona” (PBC) as a pattern linked to physiological conditions was introduced as a potential tool for the early diagnosis of cancer and other diseases [8,9]. Various authors have applied this concept to detect specific pathological stages of disease [10,11,12,13]. Efforts have been made to isolate and identify specific proteins or clusters of proteins that could be used as biomarkers [14]

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