Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy
: Zhang Jiahui, Ji Cheng, Zhang Hongbo, Shi Hui, Mao Fei, Qian Hui, Xu Wenrong, Wang Dongqing, Pan Jianming, Fang Xinjian, Santos Helder A., Zhang Xu
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
: 2022
: Science Advances
: SCIENCE ADVANCES
: SCI ADV
: eabj8207
: 8
: 2
: 13
: 2375-2548
DOI: https://doi.org/10.1126/sciadv.abj8207
: https://www.science.org/doi/10.1126/sciadv.abj8207
: https://research.utu.fi/converis/portal/detail/Publication/174776743
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.
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