Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu, 215123, P. R. China.
Small. 2021 Dec;17(52):e2104773. doi: 10.1002/smll.202104773. Epub 2021 Nov 2.
Tumor radiofrequency ablation (RFA) is a local and minimally invasive application using high temperature to induce coagulative necrosis of tumor, which has been commonly used in clinic. Although the tumor fragments generated by RFA can activate the host's immune system, it may be insufficient to inhibit cancer recurrence due to many factors such as the inefficient antigen presentation by dendritic cells (DCs). In this research, a convenient local administration strategy by blocking rho-associated kinases (ROCK) is applied to amplify the immune responses triggered by RFA via promoting the phagocytosis capacity of DCs. Briefly, ROCK inhibitor, Y27632, is successfully dispersed in the amphiphilic copolymer poly(D,L-lactide-co-glycolide)-b-poly(ethyleneglycol)-b-poly(D,L-lactideco-glycolide) (PLGA-PEG-PLGA) solution, which is sol at room temperature and forms hydrogel quickly at body temperature, obviously prolonging the retention of Y27632 after injection. Interestingly, in the melanoma tumor model, the generated tumor fragments after RFA treatment are swallowed by DCs and undergo reinforced antigen presentation process with the help of gradual released Y27632, further effectively activating T cell mediated anti-tumor immune responses and significantly improving the therapeutic efficiency of RFA. Overall, such strategy remarkably prolongs the survival of mice after RFA treatment, showing great potential for clinical translation as an improvement strategy for RFA.
肿瘤射频消融（RFA）是一种局部微创应用，利用高温诱导肿瘤发生凝固性坏死，已广泛应用于临床。虽然 RFA 产生的肿瘤碎片可以激活宿主的免疫系统，但由于树突状细胞（DCs）抗原提呈效率低下等多种因素，可能不足以抑制癌症复发。在这项研究中，通过阻断 rho 相关激酶（ROCK）应用一种方便的局部给药策略，通过促进 DCs 的吞噬能力来放大 RFA 引发的免疫反应。简而言之，ROCK 抑制剂 Y27632 成功分散在两亲性共聚物聚（D，L-丙交酯-co-乙交酯）-b-聚（乙二醇）-b-聚（D，L-丙交酯-co-乙交酯）（PLGA-PEG-PLGA）溶液中，该溶液在室温下为溶液，在体温下迅速形成水凝胶，明显延长了注射后 Y27632 的保留时间。有趣的是，在黑色素瘤肿瘤模型中，RFA 治疗后产生的肿瘤碎片被 DCs 吞噬，并在逐渐释放的 Y27632 的帮助下经历强化的抗原呈递过程，进一步有效激活 T 细胞介导的抗肿瘤免疫反应，显著提高 RFA 的治疗效果。总的来说，这种策略显著延长了 RFA 治疗后小鼠的存活时间，为作为 RFA 改进策略的临床转化提供了巨大潜力。
