Human Breast Tumor-associated Endothelial Cells Favor Interactions with Nanomedicines

Nanomedicines, designed to improve the effectiveness of cancer treatment, have not met anticipated outcomes owing to suboptimal delivery efficiency to tumors. While the enhanced permeability and retention (EPR) effect has been explored, recent research challenges the predominant passive accumulation theory. This study explores the mechanisms governing nanoparticle entry into tumors by comparing human breast tumor-associated endothelial cells (HBTECs) and healthy human mammary macrovascular endothelial cells (HMMECs). Our results demonstrate that HBTECs exhibit higher nanoparticle uptake, involving three major endocytic pathways. Gene expression analysis reveals the upregulation of transport-related genes, especially motor protein genes, in tumor-associated endothelial cells. These insights highlight the need for comprehensive investigations into nanoparticle transport mechanisms and associated factors within the tumor microenvironment, essential for advancing drug delivery and therapeutic outcomes.