Thermosensitive selenium hydrogel boosts antitumor immune response for hepatocellular carcinoma chemoradiotherapy
Thermosensitive selenium hydrogel boosts antitumor immune response for hepatocellular carcinoma chemoradiotherapy
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DOI：
10.1016/j.nantod.2023.101823
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发表时间：
2023-06
期刊：
影响因子：
17.4
通讯作者：
Chang Liu;Run Lin;Haoqiang Lai;Fen Pi;Qian Xue;Tianfeng Chen;Wei-zhi He
中科院分区：
文献类型：
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作者：
Chang Liu;Run Lin;Haoqiang Lai;Fen Pi;Qian Xue;Tianfeng Chen;Wei-zhi He
肝细胞癌（Hepatocellular carcinoma，HCC）死亡率高，已成为恶性肿瘤死亡的第三大原因。原位载药温敏水凝胶由于具有载药量高、缓释性能好等上级优点，在肝癌治疗中受到越来越多的关注。本研究以泊洛沙姆407（P407）和载DOX的硒纳米粒子（PPS-SeNPs@DOX）为基础，构建了一种新型的原位注射温敏水凝胶系统，用于肝癌的局部协同放化疗。所合成的PPS-SeNPs@DOX水凝胶体系在32 ℃具有较好的相变温度，且在X射线照射下力学性能不受影响，表明所合成的水凝胶具有较好的稳定性。局部注射PPS-SeNPs@DOX联合放疗可显著抑制HepG 2肿瘤的生长，肿瘤体积、重量和Ki 67表达均明显降低。此外，PPS-SeNPs@DOX和X射线联合治疗原位Hepa 1 -6肿瘤时也发现了协同抗肿瘤效应，并参与了抗肿瘤免疫激活，伴随着单肽原位注射后CD 8 +T，M1和NK1.1细胞群的上调和Gr 1细胞群的下调。因此，本研究提出了一种新的原位注射温敏水凝胶系统用于肝癌的放化疗，这可能为设计用于不可切除肝癌治疗的局部给药平台提供坚实的基础。
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 situthermosensitive 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 novelin situinjection 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 growthin 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 singlein situinjection. Taken together, this study presents a novelin situinjection thermosensitive hydrogel system for the chemoradiotherapy of HCC, which may provide a solid foundation for designing local delivery platform for unresectable HCC therapy.