Thermosensitive selenium hydrogel boosts antitumor immune response for hepatocellular carcinoma chemoradiotherapy

Hepatocellular carcinoma (HCC) possesses high mortality rate and becomes the third most common cause of cancer death. Searching new therapeutic strategies for HCC are still urgently needed. In situ thermosensitive hydrogels loading with chemotherapeutics have attracted increasing attention for HCC due to their superior advantages including high drug loading and sustained drug release behavior. Herein, we developed a novel in situ injection thermosensitive hydrogel system based on Poloxamer 407 (P407) and selenium nanoparticle loading with DOX (PPS-SeNPs@DOX) for localized synergistic chemoradiotherapy of HCC. The synthesized PPS-SeNPs@DOX hydrogel system showed a better phase transition temperature at 32 ℃, and the mechanical properties were not affected under X-ray irradiation, which suggests the stability of the synthesized hydrogel. The localized injection of PPS-SeNPs@DOX combined with radiotherapy was found to significantly suppress HepG2 tumors growth in vivo, as evidenced by the decreased tumor volume, tumor weight and Ki67 expression. Furthermore, the synergistic anticancer effects in orthotopic Hepa1-6 tumors were also found in the combination treatment of PPS-SeNPs@DOX and X-ray irradiation with the involvement of antitumor immunity activation accompanied by the upregulated population of CD8+ T, M1 and NK1.1 cells and downregulated population of Gr1 cells after single in situ injection. Taken together, this study presents a novel in situ injection thermosensitive hydrogel system for the chemoradiotherapy of HCC, which may provide a solid foundation for designing local delivery platform for unresectable HCC therapy.