Local Administration of Liposomal Quantum Dots to Injured Carotid Arteries Allows Extended Macrophage Detection

Inflammation characterizes several pathological disorders including restenosis, re-obstruction of the artery following vascular injury. The inflammatory cascade involves infiltration of phagocytic cells to the injured artery, which can be exploited for delivering a cargo for theranostic use. Quantum Dots (QDs), fluorescent nano-crystals, are of great interest as imaging markers in biological and medical research. However, their biocompatibility and systemic biodistribution impedes their use. This work examined the accumulation and retention of liposomal-QDs (LipQDs), in the injured arterial wall, following local administration. LipQDs formulation was prepared by encapsulating negatively charged QDs in positively charged liposomes. The uptake and cytotoxicity were examined in murine monocyte/macrophage, smooth muscle and endothelial cell lines, the major cellular components in vascular injury. In a rat model of vascular injury, 50 µl of LipQDs was administered locally for 15 min immediately after carotid injury. A substantial fluorescent signal was observed, for at least 24 h, after local incubation of the carotid artery lumen with LipQDs, indicating both high accumulation and fluorescent stability. In contrast, accumulation of QDs following incubation with free QDs suspension was not detected, at all time points, in the injured artery. These findings were also corroborated by assessing the cadmium concentration at the injured arterial segment. In addition, an increased number of phagocytic cells were observed post injury at the injured site, peaking at 24 h. Interestingly, immuno-histochemical examination of arterial sections revealed an exclusive co-localization of LipQDs with newly-recruited macrophages, suggesting in-situ uptake of LipQDs. Our findings could pave the way to a better understanding of monocytes recruitment to the inflamed artery following vascular interventions.