Optically traceable PLGA-silica nanoparticles for cell-triggered doxorubicin delivery

Fluorescent silica nanoparticles with a polymer shell of poly (D, L-lactide-co-glycolide) (PLGA) can provide traceable cell-triggered delivery of the anticancer drug doxorubicin (DOX), protecting the cargo while in transit and releasing it only intracellularly. PLGA with 50:50 lactide:glycolide ratio was grown by surface-initiated ring-opening polymerization (ROP) from silica nanoparticles of ca. 50 nm diameter, doped with a perylenediimide (PDI) fluorescent dye anchored to the silica structure. After loading DOX, release from the core-shell particles was evaluated in solution at physiological pH (7.4), and in human breast cancer cells (MCF-7) after internalization. The hybrid silica-PLGA nanoparticles can accommodate a large cargo of DOX, and the release in solution (PBS) due to PLGA hydrolysis is negligible for at least 72 h. However, once internalized in MCF-7 cells, the nanoparticles release the DOX cargo by degradation of the PLGA. Accumulation of DOX in the nucleus causes cell apoptosis, with the drug-loaded nanoparticles found to be as potent as free DOX. Our fluorescently traceable hybrid silica-PLGA nanoparticles with cell-triggered cargo release offer excellent prospects for the controlled delivery of anticancer drugs, protecting the cargo while in transit and efficiently releasing the drug once inside the cell.