Zhang Jiahui, Ji Cheng, Zhang Hongbo, Shi Hui, Mao Fei, Qian Hui, Xu Wenrong, Wang Dongqing, Pan Jianming, Fang Xinjian, Santos Hélder A, Zhang Xu
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 212013 Zhenjiang, China.
Pharmaceutical Sciences Laboratory, Åbo Akademi University, 20520 Turku, Finland.
Sci Adv. 2022 Jan 14;8(2):eabj8207. doi: 10.1126/sciadv.abj8207. Epub 2022 Jan 12.
Neutrophils are the most abundant innate immune cells in human circulation; however, their derived exosomes have been rarely studied for tumor treatment. Here, we reported that exosomes from neutrophils (N-Ex) induce tumor cell apoptosis by delivering cytotoxic proteins and activating caspase signaling pathway. In addition, we decorated N-Ex with superparamagnetic iron oxide nanoparticles (SPIONs) to achieve higher tumor-targeting therapeutic effect. We further fabricated exosome-like nanovesicles from neutrophils (NNVs) at high yield. Compared with liposome-loaded doxorubicin (DOX) and natural NNVs, DOX-loaded NNVs show an improved inhibition of tumor cell proliferation. Moreover, DOX-loaded, SPION-decorated NNVs selectively accumulate at the tumor sites under an external magnetic field, effectively restraining tumor growth and extensively prolonging the survival rate in mice. Overall, a simple and effective method to engineer N-Ex and NNVs at clinical applicable scale was developed, which enables the efficient and safe drug delivery for targeted and combined tumor therapy.
中性粒细胞是人体循环中最丰富的固有免疫细胞；然而，它们衍生的外泌体在肿瘤治疗方面鲜有研究。在此，我们报道中性粒细胞来源的外泌体（N-Ex）通过递送细胞毒性蛋白和激活半胱天冬酶信号通路诱导肿瘤细胞凋亡。此外，我们用超顺磁性氧化铁纳米颗粒（SPIONs）修饰N-Ex以实现更高的肿瘤靶向治疗效果。我们进一步高产率地从中性粒细胞制备了类外泌体纳米囊泡（NNV）。与脂质体负载阿霉素（DOX）和天然NNV相比，负载DOX的NNV对肿瘤细胞增殖的抑制作用有所改善。此外，负载DOX且经SPION修饰的NNV在外加磁场下选择性地在肿瘤部位积聚，有效抑制肿瘤生长并显著延长小鼠的存活率。总体而言，我们开发了一种在临床适用规模上工程化改造N-Ex和NNV的简单有效方法，该方法能够实现高效且安全的药物递送，用于靶向和联合肿瘤治疗。
