Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy

Jiahui Zhang, Cheng Ji, Hongbo Zhang, Hui Shi, Fei Mao, Hui Qian, Wenrong Xu, Dongqing Wang, Jianming Pan, Xinjian Fang, Hélder A. Santos, Xu Zhang

Research output: Contribution to journalArticleScientificpeer-review

115 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article numbereabj8207
JournalScience Advances
Volume8
Issue number2
DOIs
Publication statusPublished - 14 Jan 2022
MoE publication typeA1 Journal article-refereed

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