Development of drug loaded nanoparticles for tumor targeting. Part 2: Enhancement of tumor penetration through receptor mediated transcytosis in 3D tumor models.

ABSTRACT: We report that receptor mediated transcytosis can be utilized to facilitate tumor penetration by drug loaded nanoparticles (NPs). We synthesized hyaluronan (HA) coated silica nanoparticles (SNPs) containing a highly fluorescent core to target CD44 expressed on the cancer cell surface. Although prior studies have primarily focused on CD44 mediated endocytosis to facilitate cellular uptake of HA-NPs by cancer cells, we discovered that, once internalized, the HA-SNPs could be transported out of the cells with their cargo. The exported NPs could be taken up by neighboring cells. This enabled the HA-SNPs to penetrate deeper inside tumors and reach a much greater number of tumor cells in 3D tumor models, presumably through tandem cycles of CD44 mediated endocytosis and exocytosis. When doxorubic

SUBMITTER: El-Dakdouki MH 

PROVIDER: S-EPMC3643122 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature