One of the major success determinants in targeted in vivo drug delivery using SPIONs is the adequacy of magnetic gradient. This can be partially achieved by using superconducting magnets, local implantation of magnets and application of magnetic stents. Other issues that must be considered include the pharmacokinetics and in vivo fate of SPIONs, their biodegradability, biocompatibility, potential side effects and the crucial impact of protein corona on either drug release profile or mistargeting. Surface modification of SPIONs can open up the possibility of drug delivery to intracellular organelles, drug delivery across the blood-brain barrier, modifying metabolic diseases and a variety of other multimodal and/or theranostic applications.

Various factors, including drugs as well as non-molecular influences, induce alterations in the stability of proteins in cell lysates, living cells and organisms. These alterations can be probed by applying a stability-modifying agent, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or factor intensity can be used. However, the corresponding analysis scheme has a low throughput and high cost. Additionally, since traditional data analysis employs curve fitting, proteins with unusual behavior are frequently ignored. The novel Proteome Integral Stability Alteration (PISA) assay avoids these issues altogether, increasing the analysis throughput by one to two orders of magnitude for unlimited number of parameter variation points. The consumption of the compound and biological material decreases by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development..

Robust characterization of the protein corona—the layer of proteins that spontaneously forms on the surface of nanoparticles immersed in biological fluids—is vital for prediction of the safety, biodistribution, and diagnostic/therapeutic efficacy of nanomedicines. Protein corona identity and abundance characterization is entirely dependent on liquid chromatography coupled to mass spectroscopy (LC-MS/MS), though the variability of this technique for the purpose of protein corona characterization remains poorly understood. Here we investigate the variability of LC-MS/MS workflows in analysis of identical aliquots of protein coronas by sending them to different proteomics core-facilities and analyzing the retrieved datasets. While the shared data between the cores correlate well, there is considerable heterogeneity in the data retrieved from different cores. Specifically, out of 4022 identified unique proteins, only 73 (1.8%) are shared across the core facilities providing semiquantitative analysis. These findings suggest that protein corona datasets cannot be easily compared across independent studies and more broadly compromise the interpretation of protein corona research, with implications in biomarker discovery as well as the safety and efficacy of our nanoscale biotechnologies.