On-Demand Macroscale Delivery System Based on a Macroporous Cryogel with a High Drug Loading Capacity for Enhanced Cancer Therapy

Abstract

The macroscale delivery system has been one of the practical platforms for a controlled delivery system by acting as a local depot close to the target tissue. In this study, we fabricated a macroporous alginate crygel incorporated with gold nanorods (GNRs) for the on-demand release of a chemotherapeutic drug from macroscale materials placed beside the target tumor. The macroporous crygel was prepared by the ice-crystal templating of a covalently crosslinked alginate hydrogel incorporated with GNRs. Mitoxantrone (MX), one of the potent anticancer drugs with a positive charge, was strongly adsorbed on the negative alginate chains of the cryogels. This system enabled a high loading of MX and a successful on-demand release of strongly bound MX from the GNR-loaded macroporous cryogels by near-infrared (NIR) irradiation by the dissociation of the interaction between the alginate backbone and MX. Cell viability after the NIR irradiation of the MX-loaded macroporous cryogel was significantly lower compared to that under no stimuli conditions. The in vivo test showed that repetitive NIR irradiations on the MX-loaded cryogel implanted near the tumor suppressed the tumor volume six times more than that of the control group. This simple approach to fabricate a macroporous cryogel capable of the on-demand release of bioactive cargos could be beneficial in various applications including cell, gene, and the other small molecule delivery systems.

Keywords: alginate; cancer therapy; cryogel; gold nanorods; mitoxantrone; on-demand delivery.