Easy recurrence of large hepatocellular carcinoma (HCC) after microwave (MW) ablation or transarterial chemoembolization (TACE) is still very challenging. In this study, porous polylactide-co-glycolide (PLGA) microspheres as a MW-susceptible TACE agent (P-PLGA@DN microspheres) for triple-combination therapy of large HCC were developed via the double emulsion technique using recruited ions (Na+ and Cl-) and doxorubicin hydrochloride (DOX·HCl) to enhance the efficiency of MW absorption and DOX chemotherapy after tumor embolization. The as-prepared microspheres with superior MW-heat conversion can enlarge the ablation area by >53% in a simulated physiological environment. The in vivo efficiencies of chemotherapy and thermal therapy for ICR mice bearing H22 tumor cells under the assistance of P-PLGA@DN microspheres reach to 100%. In the experiments of synergistic therapy combining TACE with MW ablation on VX2 tumor-bearing New Zealand white rabbits, PLGA@DN microspheres can increase ablation area by more than 50%, enhancing the necrosis of tumor cells and effectively inhibiting tumor growth. These results demonstrate that the potential application of P-PLGA@DN microspheres in synergistic therapy of large HCC can be envisioned.

中文翻译：

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带有募集离子和阿霉素的多孔PLGA微球，用于大肝细胞癌的三联疗法。

微波（MW）消融或经动脉化学栓塞（TACE）后大肝癌（HCC）的容易复发仍然是非常具有挑战性的。在这项研究中，多孔双丙交酯-乙交酯共聚物（PLGA）微球作为一种MW易感性TACE剂（P-PLGA @ DN微球），通过采用吸收离子（Na +和N +）的双重乳化技术开发，用于大型HCC的三联疗法。 Cl-）和盐酸阿霉素（DOX·HCl）可提高肿瘤栓塞后的MW吸收和DOX化疗的效率。在模拟的生理环境中，具有优异的MW-热转化率的微球可以将消融面积扩大> 53％。在P-PLGA @ DN微球的辅助下，对带有H22肿瘤细胞的ICR小鼠进行化学疗法和热疗法的体内效率达到100％。在TACE与MW消融联合治疗VX2荷瘤新西兰白兔的协同治疗实验中，PLGA @ DN微球可将消融面积增加50％以上，增强肿瘤细胞的坏死并有效抑制肿瘤生长。这些结果表明，可以设想P-PLGA @ DN微球在大型HCC的协同治疗中的潜在应用。