Size effect of magnetic core-shell nanodrugs on efficiency of targeted cell uptake and drug delivery

Abstract

Nanoparticle size plays an important role in the cellular uptake and anticancer efficacy for targeting drug delivery. However, little research has been done on the effect of nanoparticle size on the targeting agent binding, drug loading and releasing, cytotoxicity and so on. In this work, benzoboroxole modified core-shell magnetic nanoparticles (MPA_n NPs) with four different sizes were fabricated by reflux-precipitation polymerization. Transferrin (Tf) was used as a targeting ligand and covalently immobilized on the nanoparticle surface through the reaction with benzoboroxole moieties. Then, therapeutic drug doxorubicin (DOX) was encapsulated in the polymer shell network via electrostatic interaction for preparation of nanodrugs (MPA_n-Tf-DOX NPs). The influence of nanoparticle size on the Tf binding, drug loading and releasing, cellular uptake and in vitro cytotoxicity was systemically investigated. Increasing the nanoparticle size facilitated the Tf binding and resulted in an enhanced intracellular internalization within a certain size range. Besides, all four kinds of nanoparticles showed a high DOX encapsulating efficiency (> 80 %), and large nanoparticle size was favorable for a faster drug release. Moreover, MPA₃-Tf-DOX NPs with suitable particle size (422 nm) and Tf density (202 mg/g NPs) exhibited the best cancer cell killing performance evaluated by Tf-mediated endocytosis experiments. This study investigated the combination effects of nanoparticle size on the targeting agent modification, drug loading, cellular uptake and therapeutic efficacy, which provided the fundamental data for the nanocarrier design through structural regulation to enhance targeted delivery and anticancer applications.