Targeting strategies for superparamagnetic iron oxide nanoparticles in cancer therapy

Among various nanoparticles, superparamagnetic iron oxide nanoparticles (SPIONs) have been increasingly studied for their excellent superparamagnetism, magnetic heating properties, and enhanced magnetic resonance imaging (MRI). The conjugation of SPIONs with drugs to obtain delivery nanosystems has several advantages including magnetic targeted functionalization, in vivo imaging, magnetic thermotherapy, and combined delivery of anticancer agents. To further increase the targeting efficiency of drugs through a delivery nanosystem based on SPIONs, additional targeting moieties including transferrin, antibodies, aptamers, hyaluronic acid, folate, and targeting peptides are coated onto the surface of SPIONs. Therefore, this review summarizes the latest progresses in the conjugation of targeting molecules and drug delivery nanosystems based on SPIONs, especially focusing on their performances to develop efficient targeted drug delivery systems for tumor therapy. Some magnetic nanoparticle-based nanocarriers loaded with drugs were evaluated in patients and did not produce convincing results, leading to termination of clinical development in phase II/III. An alternative strategy for drug delivery systems based on SPIONs is the conjugation of these systems with targeting segments such as transferrin, antibodies, aptamers, hyaluronic acid, folate, and targeting peptides. These targeting moieties can be recognized by specific integrin/receptors that are overexpressed specifically on the tumor cell surface, resulting in minimizing dosage and reducing off-target effects. This review focuses on magnetic nanoparticle-based nonviral drug delivery systems with targeting moieties to deliver anticancer drugs, with an aim to provide suggestions on the development of SPIONs through discussion.