Magnetic nano-particles retrievable biodegradable hydrogel microrobot

摘要

Drug therapy using cancer-targeted drug delivery particles is widely adopted as a general anti-cancer therapy. In this approach, anticancer drug particles target mainly cancer cells, thereby reducing the side effects caused by anticancer drug particles against normal cells. However, these cancer-targeted drug delivery particles still have many risks due to uncertainty in their ability to target cancer cells. Microrobots may overcome this problem by delivering therapeutic drugs to a cancer cell target lesion via electromagnetic actuation. Generally, microrobots include an anti-cancer drug and magnetic nanoparticles (MNPs) for their electromagnetic actuation. However, the MNPs may remain and cause toxicity in the body after the drug delivery. To remedy this, we propose a new type of microrobot that can deliver an anti-cancer drug to cancer target lesion and retrieve the problematic MNPs. The proposed microrobot consists of a gelatin/poly vinyl alcohol (PVA) based hydrogel, MNPs and poly lactic-co-glycolic acid particles carrying doxorubicin (PLGA-DOX particles). The targeting and the retrieval of MNPs from the hydrogel microrobot is accomplished by a fabricated customized electromagnetic actuation (EMA) and near-infra red (NIR) integrated system. First, the hydrogel microrobot reaches a pre-determined target lesion by the magnetic field of the EMA system. Next, after NIR irradiation, the gelatin/PVA of the hydrogel microrobot is decomposed and the MNPs and PLGA-DOX drug particles are left in the target area. After the disassembled MNPs are recovered out of the target lesion by the magnetic field of the EMA system, only the PLGA-DOX particles remain in the target area. Finally, the anti-cancer drug can be released from the remaining PLGA-DOX particles and can generate a therapeutic effect in the target lesion. In this study, we fabricated the hydrogel microrobot, analyzed its characteristics (shape, size, magnetization, and drug encapsulation), verified the possibilities of targeting and disassembly of the hydrogel microrobot, and proved the retrieval of MNPs and the drug delivery from the remaining PLGA-DOX particles. Additionally, we executed the drug-releasing experiment using PLGA-DOX particles and confirmed the therapeutic effect of the hydrogel microrobot through an in vitro test using Hep3B cancer cell. We conclude that the proposed hydrogel microrobot is a new type of biocompatible microrobot with the capability of active targeting as well as toxic MNP retrieval.