杂志名称：Nature Communications
影响因子：14.7
文章题目：Nanomedicine-based co-delivery of a calcium channel inhibitor and a small molecule targeting CD47 for lung cancer immunotherapy
DOI: https://doi.org/10.1038/s41467-023-42972-2
第一作者：Yuedong Guo , Qunqun Bao, Ping Hu , Jianlin Shi
作者单位：
中国科学院上海陶瓷高性能陶瓷与超细微结构国家重点实验室
中国科学院大学材料科学与光电子工程中心
上海市第十人民医院
同济大学医学院
引用YOBIBIO产品：
U30099  DC2.4(小鼠树突状细胞)

文章摘要：
Pro-tumoral macrophages in lung tumors present a significant challenge in immunotherapy. Here, we introduce a pH-responsive nanomedicine approach for activating anti-tumoral macrophages and dendritic cells. Using a layered double hydroxide nanosheet carrier, we co-deliver a T-type calcium channel inhibitor (TTA-Q6) and a CD47 inhibitor (RRX-001) into lung tumors. In the tumor acidic environment, TTA-Q6 is released, disrupting cancer cell calcium uptake, causing endoplasmic reticulum stress and inducing calreticulin transfer to the cell surface. Surface calreticulin activates macrophages and triggers dendritic cell maturation, promoting effective antigen presentation and therefore activating antitumor T cells. Simultaneously, RRX-001 reduces CD47 protein levels, aiding in preventing immune escape by calreticulin-rich cancer cells. In lung tumor models in male mice, this combined approach shows anti-tumor effects and immunity against tumor re-exposure, highlighting its potential for lung cancer immunotherapy.

肺肿瘤中的肿瘤前巨噬细胞在免疫治疗中提出了重大挑战。在这里，我们介绍了一种ph响应纳米药物方法来激活抗肿瘤巨噬细胞和树突状细胞。利用层状双氢氧化物纳米片载体，我们将t型钙通道抑制剂(TTA-Q6)和CD47抑制剂(RRX-001)共同递送到肺肿瘤中。在肿瘤酸性环境中，ta - q6被释放，破坏癌细胞钙摄取，引起内质网应激，诱导钙网蛋白向细胞表面转移。表面钙调蛋白激活巨噬细胞，触发树突状细胞成熟，促进有效抗原呈递，从而激活抗肿瘤T细胞。同时，RRX-001降低CD47蛋白水平，有助于防止富含钙调蛋白的癌细胞的免疫逃逸。在雄性小鼠的肺肿瘤模型中，这种联合方法显示出抗肿瘤作用和对肿瘤再暴露的免疫，突出了其在肺癌免疫治疗中的潜力。