Eradication of large established tumors by drug-loaded bacterial particles via a neutrophil-mediated mechanism.
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| Abstract |
The treatment of large established tumors remains a significant challenge and is generally hampered by poor drug penetration and intrinsic drug resistance of tumor cells in the central tumor region. In the present study, we developed bacterial particles (BactPs) to deliver chemotherapeutics into the tumor mass by hijacking neutrophils as natural cell-based carriers. BactPs loaded with doxorubicin, 5-fluorosuracil, or paclitaxel induced significantly greater tumor regression than unconjugated drugs. This effect was mediated by the ability of BactPs to incorporate chemotherapeutics and serve as vascular disrupting agents that trigger innate host responses and recruit phagocytic neutrophils. Vascular disruption resulted in extensive cell death in the central areas of the tumor mass. Recruited neutrophils acted as natural cellular carriers to deliver engulfed BactPs, which ensured drug delivery into the tumor mass and cytotoxic effects in areas that are normally inaccessible to traditional chemotherapy. Thus, BactPs eradicate large established tumors by functioning as vascular disrupters and natural drug carriers for neutrophil-mediated chemotherapy.
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| Authors | Gaili Ji, Qiqi Li, Yuge Shen, Jia Gan, Lin Xu, Yuxi Wang, Hui Luo, Yun Yang, E Dong, Guimin Zhang, Binrui Liu, Xiaozhu Yue, Wei Zhang, Hanshuo Yang |
| Journal | Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 334 Pg. 52-63 (06 10 2021) ISSN: 1873-4995 [Electronic] Netherlands |
| PMID | 33878368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2021 Elsevier B.V. All rights reserved. |
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