DON encapsulated carbon dot–vesicle conjugate in therapeutic intervention of lung adenocarcinoma by dual targeting of CD44 and SLC1A5
Afreen Zaman, Aparajita Ghosh, Anup K. Ghosh, Prasanta Kumar Das
Abstract
HepG2 cells and HEK 293 normal cells. Also, DON-loaded HACD-TMAV showed ∼2.0-fold higher cytotoxicity against A549 cells compared to individual carriers and ∼4.5-fold higher cytotoxicity than by DON. Furthermore, HACD-TMAV-DON induced a ∼3.5-fold reduction in the size of 3D tumor spheroids of A549 cells. The enhanced anticancer effectiveness was attributed to starvation of the A549 cells of glutamine by dual targeting of glutamine metabolism and solute linked carrier family 1 member A5 (SLC1A5) through HA-linked CD44-mediated targeted delivery of DON. This led to over-production of reactive oxygen species (ROS) that induced apoptosis of cancer cells through downregulation of the PI3K/AKT/mTOR signaling cascade.