Hybrid Iron Oxide–Graphene Oxide–Polysaccharides Microcapsule: A Micro-Matryoshka for On-Demand Drug Release and Antitumor Therapy In Vivo

Premature drug release is a common drawback in stimuli-responsive drug delivery systems (DDS), especially if it depends on internal triggers, which are hard to control, or a single external stimulus, which can only have one function. Thus, many DDS systems have been reported that combined different triggers; however, limited success has been established in fine-tuning the release process, mainly due to the poor bioavailability and complexity of the reported designs. This paper reports the design of a hybrid microcapsule (h-MC) by a simple layer-by-layer technique comprising polysaccharides (sodium alginate, chitosan, and hyaluronic acid), iron oxide, and graphene oxide (GO). Electrostatic assembly of the oppositely charged polysaccharides and graphene sheets provided a robust structure in which to load drugs through pH control. The polysaccharide component ensured high biocompatibility, bioavailability, and tumor cells targeting. The alternative magnetic field and near-infrared laser triggerable Fe3O4@GO component provided for dual high-energy and high-penetration hyperthermia therapy. On-demand drug release from h-MC can be achieved by synchronizing these external triggers, making the release highly controllable. The synergistic effect of hyperthermia and chemotherapy was successfully confirmed in vitro and in vivo.