Magnetically Actuated Drug Delivery Helical Microrobot with Magnetic Nanoparticle Retrieval Ability

Abstract

Therapeutic drug delivery microrobots capable of accurate targeting using an electromagnetic actuation (EMA) system are being developed. However, these drug delivery microrobots include a large number of magnetic nanoparticles (MNPs) for accurate EMA targeting, which causes side effects, such as problems with membrane integrity and normal cell apoptosis. Here, a biocompatible and hydrolyzable PEGDA-based drug delivery helical microrobot capable of MNP retrieval is proposed in which doxorubicin (DOX), an anticancer drug, is encapsulated and MNPs are conjugated by a disulfide bond. After being accurately delivered to the lesion of cancer cells through magnetic field manipulation, the fabricated microrobot provides rapid MNP separation and retrieval from the microrobot because of the use of dithiothreitol (DTT), a reducing agent, as an environment similar to the surrounding cancer cells and near-infrared (NIR) as an external stimulus. The characteristics of the fabricated microrobot are analyzed, and fundamental tests for active electromagnetic field manipulation, separation/retrieval of MNPs from the microrobot, and its hydrolysis are discussed. The therapeutic performance of the fabricated microrobot is verified through an in vitro test using tumor cells. Consequently, by use of an integrated system of microscope, eight-coil EMA, and NIR it is shown that the proposed microrobot can be moved to the target site by electromagnetic manipulation. The MNPs conjugated to the microrobot can be separated and retrieved, and the therapeutic effect on tumor cells by the encapsulated drug can be seen.

Keywords: disulfide bond; drug delivery microrobot; electromagnetic actuation; magnetic nanoparticle retrieval; near-infrared.