Isolation and Quantification of miRNA from the Biomolecular Corona on Mesoporous Silica Nanoparticles.

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.

Sequential pore wall functionalization in covalent organic frameworks and application to stable camptothecin delivery systems.

Post-synthetic modification of covalent organic frameworks (COFs) is strongly demanded in order to provide additional functionalities to their structures. However, the introduction of functional groups during the synthesis of two dimensional COFs (2D COFs) is highly discouraged, as they can interfere with the π-π stacking forces, compromising framework integrity. Here, we show that direct incorporation of nucleophyllic groups (e.g., primary amines) on pore wall during the synthesis of a 2D-COF (COF-5) is possible by sequential substitution of original monomers. Subsequent bonding of the antitumor drug camptothecin results in a stable hydrophobic drug delivery system. Water adsorption isotherms modelling indicates that the insertion of CPT ligand in the framework promotes a hydrophobic effect that protects a region of COF chain from boronate ester hydrolysis and resulting degradation, which is also proven by stability testing in physiological conditions. Furthermore, this hydrophobic nature favors cell internalization kinetics by promoting interactions with the lipophilic cell membrane. To the best of our knowledge, this is the first case of a stable drug delivery system based on covalently conjugated COFs.