Targeted Delivery of DNA Topoisomerase Inhibitor SN38 to Intracranial Tumors of Glioblastoma Using Sub‐5 Ultrafine Iron Oxide Nanoparticles

Effectively delivering therapeutics for treating brain tumors is hindered by the physical and biological barriers in the brain. Even with the compromised blood–brain barrier and highly angiogenic blood–tumor barrier seen in glioblastoma (GBM), most drugs, including nanomaterial‐based formulations, hardly reach intracranial tumors. This work investigates sub‐5 nm ultrafine iron oxide nanoparticles (uIONP) with 3.5 nm core diameter as a carrier for delivering DNA topoisomerase inhibitor 7‐ethyl‐10‐hydroxyl camptothecin (SN38) to treat GBM. Given a higher surface‐to‐volume ratio, uIONP shows one‐ or three‐folds higher SN38 loading efficiency (48.3 ± 6.1%, mg/mg Fe) than those with core sizes of 10 or 20 nm. SN38 encapsulated in the coating polymer exhibits pH sensitive release with