雜志名稱：Nature Communications
影響因子：14.7
文章題目：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
作者單位：
中國科學院上海陶瓷高性能陶瓷與超細微結構國家重點實驗室
中國科學院大學材料科學與光電子工程中心
上海市第十人民醫(yī)院
同濟大學醫(yī)學院
引用YOBIBIO產品：
U30099 DC2.4(小鼠樹突狀細胞)
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.
肺腫瘤中的腫瘤前巨噬細胞在免疫治療中提出了重大挑戰(zhàn)。在這里，我們介紹了一種ph響應納米藥物方法來激活抗腫瘤巨噬細胞和樹突狀細胞。利用層狀雙氫氧化物納米片載體，我們將t型鈣通道抑制劑(TTA-Q6)和CD47抑制劑(RRX-001)共同遞送到肺腫瘤中。在腫瘤酸性環(huán)境中，ta - q6被釋放，破壞癌細胞鈣攝取，引起內質網應激，誘導鈣網蛋白向細胞表面轉移。表面鈣調蛋白激活巨噬細胞，觸發(fā)樹突狀細胞成熟，促進有效抗原呈遞，從而激活抗腫瘤T細胞。同時，RRX-001降低CD47蛋白水平，有助于防止富含鈣調蛋白的癌細胞的免疫逃逸。在雄性小鼠的肺腫瘤模型中，這種聯合方法顯示出抗腫瘤作用和對腫瘤再暴露的免疫，突出了其在肺癌免疫治療中的潛力。
