Constructing an on-demand drug release system composed of thermosensitive PPP hydrogel and drug-laden alginate/graphene microspheres to treat tumorous defect

In this study, we prepared a drug-laden graphene-incorporated calcium alginate (GCA) microspheres, which were then blended with the typically thermosensitive hydrogel named poly (d,l-lactide-co-glycolide)-poly (ethylene glycol)-poly (d,l-lactide-co-glycolide) triblock copolymer (PLGA-PEG-PLGA, PPP for short) to obtain an on-demand drug controlled release system triggered by near-infrared (NIR) laser, thus achieving minimally invasive treatment of tumorous defect through the in-situ curing of the GCA/PPP hydrogel after injection into the target site. The results indicate that all these drug-laden GCA/PPP hydrogels are injectable, enabling the minimally invasive treatment of defects with complex geometries and shapes. The 2%GCA/PPP could be heated up to 45.3 ºC within 3 min under NIR irradiation and showed a unique heating plateau in the heating curve, performing the desired photothermal stability and heating-up effect in comparison with the other groups. By turning on or off the NIR irradiation, GCA/PPP hydrogels could exhibit the step-shaped drug release curves, meaning that on-demand controlling the drug release is feasible by using NIR laser as the trigger. The in vitro biological assessments showed that the drug-laden GCA/PPP hydrogels were biocompatible as well as enhanced anti-tumor capability under NIR exposure, demonstrating their promise in treatment of tumorous defects with irregular shapes.