(275d) Exploring High-Density Lipoprotein-Based Magnetic Nanoparticles As Biomimetic MRI Contrast Agents for Cancer Diagnosis

Magnetic resonance imaging (MRI) is a powerful imaging modality widely used in the diagnosis and prognosis of various disorders including cancer. To enhance the contrast between normal and pathological sites in the body and consequently improve the sensitivity and diagnostic efficacy of MRI, exogenous contrast agents (CAs) are often administered in clinical settings. Owing to their biocompatibility, and tunable physiochemical and magnetic properties, superparamagnetic iron oxide nanoparticles (SPIONs) have received considerable attention as MRI contrast agents. Current commercially available SPION-based MRI contrast agents including Resovist and Feridex, however, suffer from low sensitivity (low contrast–enhanced properties) and poor cancer specificity. To address this issue, biomimetic MRI contrast agents based on SPIONs are of particular interest not only due to their higher tumor specificity but their good sensitivity and higher biocompatibility. Here, for the first time, reconstituted high-density lipoproteins (rHDLs) were employed as biomimetic cancer delivery agents for SPIONs. HDLs are endogenous cholesterol transporters receiving much attention in biomedical applications. Incorporating rHDLs not only enhances the stability and biocompatibility of SPIONs but also provides specific cancer delivery through targeting HDLs’ receptors (scavenger receptor class B type 1 [SR-B1]) overexpressed on a variety of cancer cells including prostate cancer.

In this study, Hydrophobic SPIONs were synthesized through a thermal decomposition process, and subsequently, SPION-loaded rHDLs were prepared according to the solvent evaporation procedure. The obtained SPIONs and SPION-loaded rHDLs had the average hydrodynamic size of 15-40 nm and 100 nm, respectively, with PDI < 0.2. The synthesized nanoparticles were further characterized in terms of composition, size, polydispersity index (PDI), ζ-potential, and X-ray diffraction. The encapsulation efficiency of SPION-loaded rHDLs was determined to be 80%, and their high stability was confirmed upon incubation in 10% FBS RPMI-1640 cell culture media as a physiologically relevant microenvironment. Their superior MRI contrast-enhanced properties compared to the conventional MRI contrast agents were demonstrated using 3T MRI. Moreover, their cancer-targeting capability was evaluated by in vitro studies in which a significantly higher uptake of SPION-loaded rHDLs was shown by PC3 and LNCAP prostate cancer cells compared to the normal cells. Finally, the cytotoxicity studies demonstrated >86% viability of CHO cells and normal prostate cells after 72 h incubation with SPION-loaded rHDLs at the Fe concentration of 0−200 μg/mL validating their high biocompatibility.

All in all, this work proposed a biomimetic MRI contrast agent based on magnetic nanoparticles for cancer diagnosis. The incorporation of SPIONs into rHDLs results in a nanostructure with biomimetic properties, high stability, high biocompatibility, superior contrast-enhanced properties, and cancer targeting capability which could overcome current issues of MRI contrast agents and provide safe and efficient cancer diagnosis.