Beta-cyclodextrin decorated hyaluronic acid-coated SPIONs for improved delivery of temozolomide

Although temozolomide (TMZ) is routinely used in the treatment of glioblastoma multiforme, it is characterized by low stability, a short half-life, and serious side effects. Therefore, a new system for the effective, targeted delivery of TMZ based on superparamagnetic iron oxide nanoparticles (SPION) has been proposed. The nanoparticles were coated with hyaluronic acid, which acted as a stabilizing shell and targeting unit capable of effectively interacting with glioblastoma cells via the CD44 receptor. TMZ was introduced onto the surface of SPION by forming an inclusion complex with covalently bound beta-cyclodextrin. The drug was released gradually, in a controlled manner, for 48 h under physiological conditions. The carrier and the final delivery system both showed no hemolytic activity or toxicity towards hPBMC cells. In glioblastoma cells, TMZ-containing SPIONs were effectively taken up and induced cell cycle arrest as well as proliferation inhibition due to DNA damage. At the same time, the obtained TMZ-containing nanoparticles did not show toxicity towards normal human cells. Importantly, thanks to the unique magnetic properties of SPIONs, they also offer additional advantages of MRI imaging and magnetic guidance. The proposed delivery system, characterized by prolonged TMZ release, a good safety profile, and strong antitumor activity, is a promising candidate for targeted TMZ delivery.