PLGA Nanoparticles Loaded with Sorafenib Combined with Thermosensitive Hydrogel System and Microwave Hyperthermia for Multiple Sensitized Radiotherapy

Abstract

Hypoxia is typically the leading cause of radiotherapy (RT) resistance in solid tumors, and glutathione (GSH) overexpression in tumor cells is a potent antioxidant mechanism that protects tumor cells from radiation damage. Herein, we developed a sorafenib (SFN) loaded-PLGA hydrogel system (SPH) in combination with microwave (MW) hyperthermia for RT sensitization. SPH with stable properties was produced by combining SFN and PLGA in a specific ratio and encapsulating the mixture in agarose hydrogel. Intratumoral injection of SPH to mice combined with MW hyperthermia can not only directly cause thermal damage to tumor cells, but also increase blood oxygen delivery to the tumor site, thus overcoming the problem of intratumoral hypoxia and achieving “first layer” RT sensitization. Moreover, high temperatures can cause the hydrogel to disintegrate and release SFN. Not only can SFN inhibit tumor growth, but it can also achieve the “second layer” of RT sensitization by inhibiting glutathione (GSH) synthesis in cells and increasing reactive oxygen species (ROS) production. Experiments, both in vitro and in vivo, have indicated that SPH and MW hyperthermia can achieve a double RT sensitization effect and a significant tumor inhibition effect. In conclusion, combining our SPH nanosystem and thermoradiotherapy is a promising anti-tumor treatment.

Targeting nanoplatform synergistic glutathione depletion-enhanced chemodynamic, microwave dynamic, and selective-microwave thermal to treat lung cancer bone metastasis

“…These results shown the excellent microwave heating effect of MgFe 2 O 4 NPs in the simulated body fluid and laid the determining the concentration and microwave power in subsequent experiments. It has been reported that temperatures ranging from 43 to 48 °C can induce apoptosis and necrosis in tumor cells [ 60 ]. The 5 W and 6 W groups met the temperature requirement for damaging tumor cells, and the power of the 6 W group was not acceptable due to easy damage to the surrounding tissue.…”