金属离子-海藻酸盐水凝胶可增强微波肿瘤消融以协同治疗癌症

SCI

10 September 2022

Metallo-alginate hydrogel can potentiate microwave tumor ablation for synergistic cancer treatment

Zhu Y, Yang Z, Pan Z, Hao Y, Wang C, Dong Z, Li Q, Han Y, Tian L, Feng L, Liu Z. Metallo-alginate hydrogel can potentiate microwave tumor ablation for synergistic cancer treatment. Sci Adv. 2022 Aug 5;8(31):eabo5285. doi: 10.1126/sciadv.abo5285. Epub 2022 Aug 3. PMID: 35921425; PMCID: PMC9348787.

Abstract  

Microwave ablation (MWA) as a local tumor ablation strategy suffers from posttreatment tumor recurrence. Development of adjuvant biomaterials to potentiate MWA is therefore of practical significance. Here, the high concentration of Ca2+ fixed by alginate as Ca2+-surplus alginate hydrogel shows enhanced heating efficiency and restricted heating zone under microwave exposure. The high concentration of extracellular Ca2+ synergizes with mild hyperthermia to induce immunogenic cell death by disrupting intracellular Ca2+ homeostasis. Resultantly, Ca2+-surplus alginate hydrogel plus MWA can ablate different tumors on both mice and rabbits at reduced operation powers. This treatment can also elicit antitumor immunity, especially if synergized with Mn2+, an activator of the stimulation of interferon genes pathway, to suppress the growth of both untreated distant tumors and rechallenged tumors. This work highlights that in situ-formed metallo-alginate hydrogel could act as microwave-susceptible and immunostimulatory biomaterial to reinforce the MWA therapy, promising for clinical translation.

微波消融（MWA）作为一种局部肿瘤消融策略，治疗后肿瘤复发。因此，开发增强 MWA 的辅助生物材料具有实际意义。在这里，高浓度的 Ca2+ 被海藻酸盐固定为 Ca2+-剩余藻酸盐水凝胶，在微波暴露下显示出提高的加热效率和受限的加热区。高浓度的细胞外 Ca2+ 与温和的热疗协同作用，通过破坏细胞内 Ca2+ 稳态来诱导免疫原性细胞死亡。结果，Ca2+-过剩的海藻酸盐水凝胶加 MWA 可以在降低手术功率的情况下消融小鼠和兔身上的不同肿瘤。这种治疗还可以引发抗肿瘤免疫，特别是如果与 Mn2+（干扰素基因通路刺激的激活剂）协同作用，可以抑制未治疗的远处肿瘤和复发肿瘤的生长。这项工作强调了原位形成的金属藻酸盐水凝胶可以作为微波敏感和免疫刺激的生物材料来加强 MWA 治疗，有望用于临床转化。

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