State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Central Laboratory, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Adv Mater. 2023 Apr;35(17):e2208546. doi: 10.1002/adma.202208546. Epub 2023 Mar 15.
Immunotherapy shows immense promise for improving cancer treatment. Combining immunotherapy with radiotherapy provides a conspicuous advantage due to its enhanced abscopal effect. However, established immune tolerance mechanisms in the tumor microenvironment can hamper the generation of a sufficient abscopal effect. Herein, a type of DNA nanocluster (DNAnc) that is self-assembled by a CpG-ODNs-loaded Y-shaped double-stranded DNA vector based on the unique complementary base-pairing rules is designed. The unique structure of DNAnc makes it load more than ≈8125.5 ± 822.5 copies of CpG ODNs within one single nanostructure, which effectively increases resistance to nuclease degradation and elevates the efficiency of repolarizing macrophages to an M1-like phenotype. Mechanistic studies reveal that more DNAncs are endocytosed by macrophages in the cancer tissue and repolarized macrophages to elicit a robust abscopal effect with the accumulation of macrophages induced by radiotherapy, generating potent, long-term, and durable antitumor immunity for the inhibition of tumor metastasis and the prevention of tumor recurrence, which provides a novel strategy to boost cancer immunotherapy.
免疫疗法在改善癌症治疗方面显示出巨大的潜力。免疫疗法与放射疗法相结合具有显著优势，因为它增强了远隔效应。然而，肿瘤微环境中已建立的免疫耐受机制可能会阻碍足够的远隔效应的产生。在此，设计了一种基于独特的互补碱基配对规则的 CpG-ODNs 负载 Y 形双链 DNA 载体自组装的 DNA 纳米簇（DNAnc）。DNAnc 的独特结构使其在单个纳米结构内可负载超过 ≈8125.5 ± 822.5 个 CpG ODN，这有效地提高了对核酸酶降解的抵抗力，并提高了重极化巨噬细胞向 M1 样表型的效率。机制研究表明，更多的 DNAncs 被癌症组织中的巨噬细胞内吞，并使巨噬细胞重极化，从而引发强烈的远隔效应，与放射治疗诱导的巨噬细胞积累一起，产生强大、持久和持久的抗肿瘤免疫，以抑制肿瘤转移和预防肿瘤复发，为增强癌症免疫疗法提供了一种新策略。
