Macrophage Reprogramming with Anti-miR223-Loaded Artificial Protocells Enhances In Vivo Cancer Therapeutic Potential.
Macrophage Reprogramming with Anti-miR223-Loaded Artificial Protocells Enhances In Vivo Cancer Therapeutic Potential.
复制标题
DOI：
10.1002/advs.202202717
复制
发表时间：
2022-12
期刊：
影响因子：
15.1
通讯作者：
Martin, Paul
中科院分区：
文献类型：
--
作者：
Lopez-Cuevas, Paco;Xu, Can;Severn, Charlotte E.;Oates, Tiah C. L.;Cross, Stephen J.;Toye, Ashley M.;Mann, Stephen;Martin, Paul
几种免疫细胞表达的miRNAs（miRs）与癌症患者预后结果的改变有关，这表明它们可能是开发癌症治疗的潜在靶点。在这里，半透明的斑马鱼（Danio rerio）被用来证明，一种这样的miR，microRNA-223（miR 223）的基因敲除或敲低，全球或特异性地在白细胞中，确实导致癌症进展减少。作为潜在转化为临床治疗的第一步，描述了一种新的策略，用于利用微型人工原始细胞（PC）重编程中性粒细胞和巨噬细胞，以针对抗炎miR 223递送抗miRs。使用遗传和活体成像方法，显示斑马鱼中白细胞对负载抗miR 223的PC的吞噬摄取（以及体外人巨噬细胞）通过阻断促炎细胞因子的抑制有效地抑制其促炎状态，反过来，改变免疫细胞与癌细胞的相互作用，并通过减少肿瘤细胞的增殖和增加肿瘤细胞的死亡，最终降低癌症负担。细胞这种将白细胞重编程为有益表型的PC货物递送策略也对治疗其他全身或局部免疫介导的病理具有意义。白细胞具有显著的癌症监视能力，因此将它们从癌症培育方向重新编程并朝向癌症杀伤方向是一种治疗愿望。这项研究报告了静脉内（或直接）注射载有抗microRNA-223货物的微型人工原始细胞如何重新编程幼虫和成年斑马鱼中的癌症相关巨噬细胞，使其更具促炎性，从而能够驱动黑色素瘤缩小。
Several immune cell‐expressed miRNAs (miRs) are associated with altered prognostic outcome in cancer patients, suggesting that they may be potential targets for development of cancer therapies. Here, translucent zebrafish (Danio rerio) is utilized to demonstrate that genetic knockout or knockdown of one such miR, microRNA‐223 (miR223), globally or specifically in leukocytes, does indeed lead to reduced cancer progression. As a first step toward potential translation to a clinical therapy, a novel strategy is described for reprogramming neutrophils and macrophages utilizing miniature artificial protocells (PCs) to deliver anti‐miRs against the anti‐inflammatory miR223. Using genetic and live imaging approaches, it is shown that phagocytic uptake of anti‐miR223‐loaded PCs by leukocytes in zebrafish (and by human macrophages in vitro) effectively prolongs their pro‐inflammatory state by blocking the suppression of pro‐inflammatory cytokines, which, in turn, drives altered immune cell‐cancer cell interactions and ultimately leads to a reduced cancer burden by driving reduced proliferation and increased cell death of tumor cells. This PC cargo delivery strategy for reprogramming leukocytes toward beneficial phenotypes has implications also for treating other systemic or local immune‐mediated pathologies. Leukocytes have remarkable cancer surveillance capacities and so reprogramming them away from cancer nurturing and toward cancer killing is a therapeutic aspiration. This study reports how intravenous (or direct) injection of miniature artificial protocells loaded with anti‐microRNA‐223 cargo can reprogram cancer‐associated macrophages in larval and adult zebrafish leading them to be more pro‐inflammatory and thus able to drive melanoma shrinkage.
登录
查看更多内容
影响因子：
10.1
作者：
Heideveld E;Hampton-O'Neil LA;Cross SJ;van Alphen FPJ;van den Biggelaar M;Toye AM;van den Akker E
通讯作者：
van den Akker E
影响因子：
9.2
作者：
Feng, Yi;Renshaw, Stephen;Martin, Paul
通讯作者：
Martin, Paul
影响因子：
15
作者：
Huang, Xin;Patil, Avinash J.;Mann, Stephen
通讯作者：
Mann, Stephen
影响因子：
3.5
作者：
Eichelberger, LE;Koch, MO;Cheng, L
通讯作者：
Cheng, L
影响因子：
1.2
作者：
Benard, Erica L.;van der Sar, Astrid M.;Meijer, Annemarie H.
通讯作者：
Meijer, Annemarie H.