Scientists at the University of Toronto have developed a new theory that explains how nanoparticles enter and exit tumors, potentially challenging the current understanding of cancer nanomedicine that has guided research for nearly four decades. The prevailing theory, known as the Enhanced Permeability and Retention (EPR) effect, suggests that nanoparticles enter tumors through gaps in the endothelial cells lining the blood vessels and become trapped due to dysfunctional lymphatic vessels. However, the new study, led by Matthew Nguyen from Professor Warren Chan’s lab and published in Nature Materials, found that approximately 45% of nanoparticles that accumulate in tumors actually exit them. This discovery sheds light on why treatments based on the EPR effect have been unsuccessful in clinical trials, confirming previous research from the Chan lab that revealed less than 1% of nanoparticles reach tumors. Contrary to the EPR effect, the scientists discovered that nanoparticles can leave tumors via the lymphatic vessels, with the exit route depending on the size of the nanoparticles. Larger nanoparticles (50 to 100 nm wide) are more likely to exit through lymphatic vessels within the tumors, while smaller ones (up to 15 nm wide) are more likely to exit through lymphatic vessels surrounding the tumors. In rare cases, nanoparticles may also exit through blood vessels. The exit process involves spaces in the lymphatic vessel walls and transport vesicles that carry the nanoparticles through these walls. The researchers also observed that nanoparticles can re-enter the bloodstream after lymphatic drainage, hypothesizing that they may eventually return to the tumor for another opportunity to treat it. Challenging the long-standing EPR effect was a complex task that the Chan lab has been working on for several years. Prior to this study, their focus was on understanding how nanoparticles enter tumors, leading to the development of a competing theory called the Active Transport and Retention (ATR) principle. Nguyen believes that the field of nanomedicine has advanced since the publication of the nanoparticle entry study in 2020.
Date: Sep 26 2023
