Recently, Professor Wang Yucai and Associate Professor Jiang Wei from the Department of Life Science and Medicine of University of Science and Technology of China and their team, using the self-developed multi-level in vivo microscopic imaging technology, clearly pointed out for the first time that there is a dense basement membrane structure outside the tumor blood vessels, which seriously impedes the extravascular permeability of nano drugs, leading to the formation of "blood pools" of nano drugs outside the tumor blood vessels Accumulation of samples. Relevant research results were published online in Nature Nanotechnology.
Tumor blood vessels constitute the main way for nano drugs to enter tumor tissue, so the efficient delivery of nano drugs largely depends on the vascular system. The current research paradigm is mainly based on the theory of "enhanced infiltration and retention effect" first proposed in 1986. This theory believes that the tumor vascular endothelial cell barrier is the last line of defense for nano drugs to penetrate into tumor tissue, and nano drugs can use the high permeability of tumor blood vessels to cross this barrier and directly enter the tumor microenvironment.
However, the results of preclinical and clinical studies based on this theory are not satisfactory. Some research data show that nano carriers can only deliver about 0.7% of drugs to tumor tissues effectively. Is the existence of other mechanisms that are not fully understood preventing nano drugs from entering solid tumors?
Through in-depth in vivo microscopic imaging analysis, this study accurately analyzed the spatial location, microstructure and cause of formation of the "blood pool" composed of the basement membrane, and further revealed that enzymatic degradation of the basement membrane can significantly reduce the number of "blood pools", thereby enhancing the permeability of nano drugs.
The study further confirmed that the migration mechanism of neutrophils induced by inflammation can temporarily form a dynamic "window" on the basement membrane, so as to achieve the volcanic and efficient penetration of nano drugs, and effectively enhance the enrichment and therapeutic effect of nano drugs in tumor tissue.
The researchers introduced that this study not only proposed an innovative mechanism of nano drug enrichment that is different from the traditional "enhanced permeability and retention effect", but also provided new theoretical support for the application of nano drugs in tumor treatment, and refreshed people's overall understanding of the trans vascular transport mechanism of nano drugs. (Wang Min)
