Investigation of the Enhanced Permeability and Retention Effect Using Fluorescent Nanoparticles

Markstein 308

There is presently a shortage of methods to accurately identify tumor margins which contributes to the 37% mortality rate of the 1.5 million new cases of cancer reported each year [1]. The instance of cancerous cells present on edges of removed tumors (positive margins) is extremely detrimental to a patient’s outcome and impacts local recurrence. During excision, surgeons excise 2 cm around cancerous sites, but pathology can take up to two weeks to evaluate the tissue excised for positive or negative margins. We are developing a new imaging strategy to help guide surgeons in the operating room that uses fluorescent liposomal contrast agents. These nanoparticles (NPs) have the ability to passively accumulate in solid tumors due to the enhanced permeability and retention effect (EPR). Surgeons can exploit the EPR effect to accurately locate cancer in real-time and decrease positive margin rates. Liposomes are biodegradable, biocompatible, and have already been clinically translated. However, their use in vivo in relation to the EPR effect still needs to be investigated. One variable that can enhance liposomal accumulation at tumor sites is optimization of the size of nanoparticles. This project considers two sizes of nanoparticles (100 nm and 400 nm) to determine which size can best accumulate in tumors while preserving the intensity of the fluorescent dye the liposome encompasses.