Kuang Gaizhen, Zhang Qingfei, Yu Yunru, Shang Luoran, Zhao Yuanjin
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China.
Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325001, China.
Bioact Mater. 2023 Jun 6;28:326-336. doi: 10.1016/j.bioactmat.2023.05.021. eCollection 2023 Oct.
Prevention of recurrence/metastasis and tissue regeneration are critical for post-surgery treatment of malignant tumors. Here, to address these needs, a novel type of microgel co-loading cryo-shocked cancer cells, immunoadjuvant, and immune checkpoint inhibitor is presented by microfluidic electrospray technology and liquid nitrogen treatment. Owing to the encapsulation of cryo-shocked cancer cells and immunoadjuvant, the microgels can recruit dendritic cells and activate them , and evoke a robust immune response. Moreover, with the combination of the immune checkpoint inhibitor, the antitumor immune response is further enhanced by inhibiting the interaction of PD1 and PDL1. With this, the excellent anti-recurrence and anti-metastasis efficacy of the microgels are demonstrated in an orthotopic breast cancer mouse model. Besides, because of the excellent biocompatibility and appropriate degradation performance, the microgels can provide support for normal cell adhesion and growth, which is beneficial to tissue reconstruction. These properties indicate the great value of the cryo-shocked cancer cell microgels for efficient tumor postoperative combination immunotherapy and tissue regeneration.
预防复发/转移和组织再生对于恶性肿瘤的术后治疗至关重要。在此,为满足这些需求,通过微流控电喷雾技术和液氮处理,提出了一种新型微凝胶,其共负载冷冻休克癌细胞、免疫佐剂和免疫检查点抑制剂。由于冷冻休克癌细胞和免疫佐剂的封装,微凝胶可以募集树突状细胞并激活它们,引发强大的免疫反应。此外,通过免疫检查点抑制剂的联合作用,通过抑制PD1和PDL1的相互作用进一步增强了抗肿瘤免疫反应。由此,在原位乳腺癌小鼠模型中证明了微凝胶具有优异的抗复发和抗转移功效。此外,由于具有优异的生物相容性和适当的降解性能,微凝胶可以为正常细胞的粘附和生长提供支持,这有利于组织重建。这些特性表明冷冻休克癌细胞微凝胶在高效肿瘤术后联合免疫治疗和组织再生方面具有巨大价值。