Molecular Imprinting of Phospholipids for Targeted Cell and Exosome Recognition

Phospholipids, integral to the composition of cell membranes and extracellular vesicles, play a pivotal role in numerous biological processes. The precise identification, localization, and isolation of these membrane phospholipids are crucial for sophisticated imaging and liquid biopsy. However, the structural diversity and amphiphilic nature of phospholipids present significant challenges. In this study, we have developed a novel molecular imprinting strategy that integrates reversed-phase microemulsions with molecular imprinting of phosphoryl group-directed epitopes to prepare molecularly imprinted polymers (MIPs). Titanium dioxide is employed as the core material to orient the phosphoryl groups, thereby facilitating the efficient alignment of the hydrophilic polar heads and hydrophobic fatty acid tails of phospholipids at the oil-water interface and enabling specific imprinting of the polar heads of phospholipids. Utilizing various types of phospholipids as template molecules, including phosphatidylserine (PS), sphingomyelin (SM), phosphatidylethanolamine (PE), and phosphatidylcholine (PC), the synthesized MIPs exhibit high efficiency and specificity in recognition. These MIPs hold great potential for the selective recognition of plasma membranes, offering an innovative strategy for the detection of low-abundance, specific phospholipids. Furthermore, PS-MIP demonstrates high specificity for targeting particular tumor cells, making it suitable for targeted drug delivery. The application of phospholipid-imprinted MIPs enables the efficient capture of exosomes from body fluids, thereby enabling the analysis of lipid metabolites via mass spectrometry in liver disease samples at various stages of the disease. This approach holds promise for a wide range of applications in exosome-based liquid biopsies, offering a novel method for the early detection and monitoring of diseases.