Monocyte-mediated liposomal delivery systems of quantum dots for the imaging of mammary carcinoma in mice

Inflammation, a multi-factorial process that combines both cellular and non-cellular components, plays a pivotal role in the initiation, progression, and eventually resolution of many pathologies including, cardiovascular diseases, autoimmune disorders, and malignancies. The inflammatory cascade involves substantial recruitment of phagocytic cells, which can be exploited for therapeutic as well as diagnostic purposes. Charged liposomal delivery systems are preferentially phagocytized by monocytes in the blood, and the phagocytizing cells accumulate at the inflammation site. We have demonstrated that by administering quantum dots (QDs) encapsulated in positively-charged liposomes, enhanced imaging of injured arteries is achieved. In this work we examined the accumulation and retention of liposomal-QDs (LipQDs) in a mammary carcinoma model, following systemic administration.

A murine model of mammary carcinoma was used (orthotopic implantation of 4T1 cells, a xenograft model). When the tumor reached an average size of 20 mm³, LipQDs (200 µl) were injected IV on day 0, 2 and 4 . A marked fluorescent signal was observed in the tumor, 7 days after the 1^st injection, demonstrating both high accumulation and fluorescent stability. In contrast, no fluorescent signal was detected in the tumor following administration of free QDs. The enhanced tumor fluorescence was corroborated by a quantitative assay of QDs concentration in the tumor. Treatment with PEGylated liposomal-QDs (pegLipQDs), possessing different physicochemical properties and increased blood-retention time, exhibited similar accumulation in the tumor. It is suggested that accumulation of QDs in the tumor is similar following monocyte-based delivery (LipQDs) and via passive delivery by the enhanced permeability and retention effect (pegLipQD). The developed liposomal delivery systems of QDs are effective for tumor imaging.