Janus Microcarriers for Magnetic Field-Controlled Combination Chemotherapy of Hepatocellular Carcinoma

Abstract

Combination chemotherapy administering multiple chemo agents is widely exploited for the treatment of various cancers in the clinic. Specially for hepatocellular carcinoma (HCC), one of the most common malignancies, a coadministration of combinational cytostatic multikinase inhibitors and cytotoxic chemo agents has been suggested as a potential curative approach. Here, Janus microcarriers are developed for the controlled local combination chemotherapy of HCC. The Janus microcarriers are composed of a polycaprolactone (PCL) compartment and a magnetic nanoparticle-loaded poly(lactide-co-glycolic acid) (PLGA) compartment which contains hydrophobic regorafenib and hydrophilic doxorubicin, respectively. Exploiting the magnetic anisotropy, rotational motion of the Janus microcarriers is controlled with a magnetic field, which enables the active corelease of dual chemo agents. Furthermore, Janus microcarriers exhibit magnetic resonance (MR) contrast effect, supporting the successful transcatheter intra-arterial delivery of the combination chemo agents loaded in the microcarriers to the targeted tumor. This Janus microcarrier potentially serves as a general combinational chemotherapeutic platform for the codelivery of various combinations of multichemo agents.