Reconstituted High-Density Lipoprotein Based Studies On CEST Contrast Agent

High-density lipoprotein (HDL) is a kind of lipid-protein complex nanoparticles exsisting in blood vessel, and the main function of HDL is called reverse cholesterol transfer. Moreover, HDL has specificity to the SR-BI receptor expressed on macrophages. Atherosclerosis is a kind of symptom that dreadfully affects mankind’s health and also plays an important role in the progressing of cardiovascular diseases, which is the main cause of death in developed countries. It is commonly considered that the progress of atherosclerosis is related to the formation of foam cells after the macrophages enter the artery wall. Thus, it is significant for the research of the formation of atherosclerosis to achieve high-sensitive detection of macrophages. Recently, a series of contrast agents on MRI, CT and fluorescence were developed based on reconstituted HDL (rHDL) for the detection of atherosclerosis plaques.Paramagnetic chemical exchange saturation transfer (PARACEST) is a newly developed magnetic resonance method. Unlike traditional MRI methods, PARACEST is mainly based on the exchange between the bound water on Ln chelate and bulk water. When put a satuation on the bound water, the MR signal of bulk water changes because of the chemical exchange, by which the indirect detection of CEST contrast agent is achieved. However, PARACEST suffers its relative modest sensitivity and thus the application is limited. To improve the PARACEST sensitivity, there are two main solutions:one is to conjugate PARACEST probes on high molecular weight molecules; the other is to load probes on nanocarriers.We have designed and prepared a high-sensitive PARACEST MR/fluorescence dual-modal contrast agent based on rHDL, Eu-Rhod-rHDL, and PARACEST sensitivity was enhanced. The advantage of developing dual-modal contrast agent is the complementarity of PARACEST and fluorescence. To make the rHDL contrast agent CEST active, a phospholipid with Eu(Ⅲ) chelate conjugated on is synthesized, which is PARACEST active. After the self-assembly process of lipds and proteins, dual-modal rHDL contrast agent is made. Afterwards, several characterazation of rHDL were conduncted and the CEST property was determined.In comparison of traditional small molecular PARACEST agents, the detection sensitivity of Eu-Rhod-rHDL in enhanced by 129 folds, and thus expands the application range of PARACEST method. Meanwhile, the Eu-Rhod-rHDL is able to target macrophages and enter macrophages specifically. Thus the detection of macrophages was achieved. This dual-modal rHDL also has potential for the PARACEST detection of atherosclerosis.