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Platelet Membrane-Camouflaged Magnetic Nanoparticles for Ferroptosis-Enhanced Cancer Immunotherapy.
Small ( IF 13.0 ) Pub Date : 2020-04-27 , DOI: 10.1002/smll.202001704 Qin Jiang 1 , Kuang Wang 1 , Xingyu Zhang 2 , Boshu Ouyang 3 , Haixia Liu 1 , Zhiqing Pang 3 , Wuli Yang 1
Small ( IF 13.0 ) Pub Date : 2020-04-27 , DOI: 10.1002/smll.202001704 Qin Jiang 1 , Kuang Wang 1 , Xingyu Zhang 2 , Boshu Ouyang 3 , Haixia Liu 1 , Zhiqing Pang 3 , Wuli Yang 1
Affiliation
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Although cancer immunotherapy has emerged as a tremendously promising cancer therapy method, it remains effective only for several cancers. Photoimmunotherapy (e.g., photodynamic/photothermal therapy) could synergistically enhance the immune response of immunotherapy. However, excessively generated immunogenicity will cause serious inflammatory response syndrome. Herein, biomimetic magnetic nanoparticles, Fe3O4‐SAS @ PLT, are reported as a novel approach to sensitize effective ferroptosis and generate mild immunogenicity, enhancing the response rate of non‐inflamed tumors for cancer immunotherapy. Fe3O4‐SAS@PLT are built from sulfasalazine (SAS)‐loaded mesoporous magnetic nanoparticles (Fe3O4) and platelet (PLT) membrane camouflage and triggered a ferroptotic cell death via inhibiting the glutamate‐cystine antiporter system Xc− pathway. Fe3O4‐SAS @ PLT‐mediated ferroptosis significantly improves the efficacy of programmed cell death 1 immune checkpoint blockade therapy and achieves a continuous tumor elimination in a mouse model of 4T1 metastatic tumors. Proteomics studies reveal that Fe3O4‐SAS @ PLT‐mediated ferroptosis could not only induce tumor‐specific immune response but also efficiently repolarize macrophages from immunosuppressive M2 phenotype to antitumor M1 phenotype. Therefore, the concomitant of Fe3O4‐SAS @ PLT‐mediated ferroptosis with immunotherapy are expected to provide great potential in the clinical treatment of tumor metastasis.
中文翻译：
血小板膜伪装的磁性纳米粒子用于肥大症，增强型癌症的免疫治疗。
尽管癌症免疫疗法已经成为一种非常有前途的癌症疗法，但它仅对几种癌症有效。光免疫疗法（例如光动力/光热疗法）可以协同增强免疫疗法的免疫反应。但是，过度产生的免疫原性会引起严重的炎症反应综合征。在本文中，仿生磁性纳米颗粒Fe 3 O 4 -SAS @ PLT被报道为一种新的方法，用于敏化有效的肥大症和产生轻度的免疫原性，从而提高非发炎性肿瘤对癌症免疫治疗的反应率。Fe 3 O 4 ‐SAS @ PLT由载有柳氮磺胺吡啶（SAS）的中孔磁性纳米颗粒（Fe 3 O 4）和血小板（PLT）膜伪装和通过抑制谷氨酸-胱氨酸逆向转运系统X触发的ferroptotic细胞死亡Ç -通路。Fe 3 O 4 -SAS @ PLT介导的肥大症可显着提高程序性细胞死亡1免疫检查点封锁疗法的功效，并在4T1转移性肿瘤小鼠模型中实现连续消灭肿瘤。蛋白质组学研究表明，Fe 3 O 4 -SAS @ PLT介导的肥大症不仅可以诱导肿瘤特异性免疫反应，而且可以使巨噬细胞从免疫抑制M2表型重新极化为抗肿瘤M1表型。因此，伴随着Fe 3 O 4‐SAS @ PLT介导的肥大症伴免疫疗法有望在肿瘤转移的临床治疗中提供巨大潜力。
更新日期：2020-04-27
中文翻译：
血小板膜伪装的磁性纳米粒子用于肥大症，增强型癌症的免疫治疗。
尽管癌症免疫疗法已经成为一种非常有前途的癌症疗法，但它仅对几种癌症有效。光免疫疗法（例如光动力/光热疗法）可以协同增强免疫疗法的免疫反应。但是，过度产生的免疫原性会引起严重的炎症反应综合征。在本文中，仿生磁性纳米颗粒Fe 3 O 4 -SAS @ PLT被报道为一种新的方法，用于敏化有效的肥大症和产生轻度的免疫原性，从而提高非发炎性肿瘤对癌症免疫治疗的反应率。Fe 3 O 4 ‐SAS @ PLT由载有柳氮磺胺吡啶（SAS）的中孔磁性纳米颗粒（Fe 3 O 4）和血小板（PLT）膜伪装和通过抑制谷氨酸-胱氨酸逆向转运系统X触发的ferroptotic细胞死亡Ç -通路。Fe 3 O 4 -SAS @ PLT介导的肥大症可显着提高程序性细胞死亡1免疫检查点封锁疗法的功效，并在4T1转移性肿瘤小鼠模型中实现连续消灭肿瘤。蛋白质组学研究表明，Fe 3 O 4 -SAS @ PLT介导的肥大症不仅可以诱导肿瘤特异性免疫反应，而且可以使巨噬细胞从免疫抑制M2表型重新极化为抗肿瘤M1表型。因此，伴随着Fe 3 O 4‐SAS @ PLT介导的肥大症伴免疫疗法有望在肿瘤转移的临床治疗中提供巨大潜力。
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