Supramolecular Polymeric Assemblies for the Selective Depletion of Abundant Acidic Proteins in Serum.

Abstract

The analysis of low-level protein biomarkers in serum is precluded by the presence of other highly abundant serum proteins. Hence, the preliminary removal of serum albumin along with other abundant proteins in serum (i.e., immunoglobulins, transferrin, haptoglobin, α-2-macroglobulin, and apolipoproteins) is often a requirement prior to any biomarker analysis. In this work, we take advantage of the low isoelectric points (pI's) of these highly abundant proteins to selectively deplete them from serum by extraction using functionalized amphiphilic polymeric nanoassemblies. The selectivity of extraction is dependent on the pI of the protein and the extraction pH, which holds true even for extremely complex protein mixtures like serum. High extraction capacity is achieved by optimizing the extraction conditions and is found to be comparable to currently available methods for depletion. Depletion of these abundant acidic proteins allows for the enhanced detection of higher pI proteins and enables a 3 orders of magnitude increase in detection sensitivity for a putative cancer biomarker, demonstrating the utility of these polymeric assemblies for enhancing the analysis of the serum proteome.