(193c) Electroporation of Nano-Sized Quantum Dots to Track Cancer Cell Transport

Primo Vascular System (PVS) is a newly found organ and it is composed of nodes (Primo Nodes; PN) and thin vessels (Primo Vessels; PV) branching out of the PNs. PVs are mechanically fragile but more elastic than lymphatic or blood vessels. PVS is found in/on most of organs, including liver, brain, intestine, heart, inside some lymphatic and blood vessels, etc., forming an extensive network system in the entire body. The liquid inside the PVS (Primo Fluid) flows at an average velocity of 0.3 mm/s. The diameter of rabbit PVs is only in the range of 20-50 micrometers and the size of the PN is in the range of 100-1000 micrometers. Due to its small size and optically transparent nature, PVS is usually difficult to observe. There are, however, three unique properties that have been used for distinguishing PVS from blood or lymphatic vessel.  These are: the outermost layer of PV is more porous than those of blood or lymphatic vessels, taking up dye solution preferentially, a PV is composed of a bundle of multiple sub-vessels running in parallel and the nuclei of the PVS endothelial cells are rod-shaped, rather than circular.

Because the existence of the PVS system was confirmed less than ten years ago most of its roles and functions in the body are still yet to be revealed. Nevertheless, several important PVS properties are already reported and some of these are; in the primo fluid, there are cells presenting stem cell markers CD133, Oct4 and Nanog, which may imply that this system has a role in regeneration; these cells are highly populated in PNs, suggesting PNs have a role of storing these cells; PVS is more densely populated in the adipose tissue, which may be important in the study of obesity; and the PVS in the brain runs a long PV through the spinal canal, implying it to be a potential communication pathway between the brain and other organs in the body.

Another very important finding is the potential relevance of PVS to cancer. According to the animal study results using xenografts of various cancer types (lung, ovarian, skin, gastric, breast cancers, leukemia, etc.), as the cancer is formed, PVS is formed at a high density in/around the tumors. For the purpose of tracing the movement of cancer cells, cancer cells were first electroporated with nanosized near infrared quantum dots (QDs). As the cells were proliferated the new cells also carried QDs. It was found that as the cancer cells form tumors they formed PVS and cancer cells were transported via the PVs in a more actively than via lymph vessels and in some cases, secondary tumors were formed at the end of PVS started from the primary tumors.

In the future we planned to use high resolution CT and MRI with gold and iron oxide nanoparticles, respectively, as contrast agent to image the PVS in three dimensions.