Transcatheter arterial chemoembolization (TACE) exhibits an important role in the treatment of some solid tumors. However, incomplete embolization and angiogenesis-induced tumor relapse and metastasis remain the biggest challenges for TACE. Here, we synthesized metformin-conjugated poly(N-acryloyl glycinamide) (Met) nanogels for precisely synergizing TACE with radiofrequency ablation (RFA) to improve antitumor efficacy. Met nanogels exhibited RF-heating effect and UCST-type gel-sol phase transition, with high performance of sol syringeability, gel strength and thermal stability. Meanwhile, Met nanogels showed distinct cytotoxicity and suppression of CD24. By the synergistic efficacy with RF-heating, Met nanogels exhibited significant tumor regression (0.37 ± 0.5) over 36 d in H22-bearing mice. Met nanogels further down-regulated the levels of PD-1 and Tim-3 of CD8 T cells and CD25 and CD38 of CD4 T cells, suggesting their improvement on tumor immunosuppressive microenvironment. The blood-vessel embolization of Met nanogels was well validated on rabbit ear vessel model. Met nanogels provide a new paradigm for constructing RF responsive embolic platform.

中文翻译：

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射频诱导二甲双胍共轭纳米凝胶的 UCST 型凝胶-溶胶转变，用于精确协同热消融和血管栓塞


经导管动脉化疗栓塞（TACE）在一些实体瘤的治疗中发挥着重要作用。然而，栓塞不完全和血管生成引起的肿瘤复发和转移仍然是TACE面临的最大挑战。在这里，我们合成了二甲双胍缀合的聚（N-丙烯酰甘氨酰胺）（Met）纳米凝胶，用于精确协同 TACE 与射频消融（RFA）以提高抗肿瘤功效。 Met纳米凝胶表现出射频加热效应和UCST型凝胶-溶胶相变，具有高性能的溶胶可注射性、凝胶强度和热稳定性。同时，Met 纳米凝胶表现出明显的细胞毒性和 CD24 抑制作用。通过与射频加热的协同功效，Met 纳米凝胶在 H22 小鼠中在 36 天内表现出显着的肿瘤消退 (0.37 ± 0.5)。 Met纳米凝胶进一步下调CD8 T细胞的PD-1和Tim-3以及CD4 T细胞的CD25和CD38的水平，表明它们改善了肿瘤免疫抑制微环境。 Met 纳米凝胶的血管栓塞作用在兔耳血管模型上得到了很好的验证。 Met 纳米凝胶为构建射频响应栓塞平台提供了新的范例。