Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Sci Adv. 2020 Dec 9;6(50). doi: 10.1126/sciadv.abc3013. Print 2020 Dec.
Live cells have been vastly engineered into drug delivery vehicles to leverage their targeting capability and cargo release behavior. Here, we describe a simple method to obtain therapeutics-containing "dead cells" by shocking live cancer cells in liquid nitrogen to eliminate pathogenicity while preserving their major structure and chemotaxis toward the lesion site. In an acute myeloid leukemia (AML) mouse model, we demonstrated that the liquid nitrogen-treated AML cells (LNT cells) can augment targeted delivery of doxorubicin (DOX) toward the bone marrow. Moreover, LNT cells serve as a cancer vaccine and promote antitumor immune responses that prolong the survival of tumor-bearing mice. Preimmunization with LNT cells along with an adjuvant also protected healthy mice from AML cell challenge.
活细胞已被广泛设计成药物输送载体,以利用其靶向能力和货物释放行为。在这里,我们描述了一种简单的方法,通过将活癌细胞在液氮中冲击来获得含有治疗剂的“死细胞”,从而在保留其主要结构和向病变部位趋化性的同时消除其致病性。在急性髓系白血病 (AML) 小鼠模型中,我们证明了液氮处理的 AML 细胞 (LNT 细胞) 可以增强阿霉素 (DOX) 对骨髓的靶向递送。此外,LNT 细胞可用作癌症疫苗,并促进抗肿瘤免疫反应,延长荷瘤小鼠的存活时间。用 LNT 细胞和佐剂进行预免疫也可以保护健康小鼠免受 AML 细胞的攻击。