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

doi:10.1126/sciadv.abj8207

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

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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 language	English
Article number	eabj8207
Journal	Science Advances
Volume	8
Issue number	2
DOIs	https://doi.org/10.1126/sciadv.abj8207
Publication status	Published - 14 Jan 2022
MoE publication type	A1 Journal article-refereed

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10.1126/sciadv.abj8207Licence: CC BY-NC

Zhang et al., 2022 Sci AdvFinal published version, 7.5 MBLicence: CC BY

https://urn.fi/URN:NBN:fi-fe2022051736077

Åbo Akademi Functional Printing Center
Martti Toivakka (PI), Jessica Rosenholm (PI), Nicklas Anttu (PI), Johan Bobacka (PI), Tan Phat Huynh (PI), Jouko Peltonen (PI), Xiaoju Wang (PI), Carl-Eric Wilen (PI), Chunlin Xu (PI), Hongbo Zhang (PI) & Ronald Österbacka (PI)
Faculty of Science and Engineering
Facility/equipment: Facility

1 Finished
2 Active

FCFH: Finland-China Network in Food and Health Sciences
Rosenholm, J., Xu, C. & Zhang, H.
Ministry of Education and Culture
01/01/21 → 31/12/24
Project: Ministry / Government Agency
Targeted delivery of CRISPR/Cas9 for advanced liver cancer therapy through c-Myc knockout
Zhang, H.
01/09/19 → 31/08/24
Project: Academy of Finland/Other Research Councils
InFLAMES: Innovation Ecosystem based on the Immune System
Takeda, A., Marjamäki, A., Roivainen, A., Hakanen, A., Hänninen, A., Sahlgren, C., Julkunen, I., Ivaska, J., Eriksson, J., Jorma, T., Rinne, J., Knuuti, J., Westermarck, J., Jyrki, H., Gidwani, K., Elima, K., Aires, L., Elo, L. L., Hollmen, M., Johnson, M., Salmi, M., Oresic, M., Poutanen, M., Kortelainen, M., Pentikäinen, O., Raitakari, O., Jaakkola, P., Salminen, P., Taimen, P., Vallittu, P., Rantakari, P., Mattila, P., Nuutila, P., He, Q., Lahesmaa, R., De Figueiredo, R., Jalkanen, S., Lönnberg, T., Soukka, T., Salminen, T. A., Veromaa, T., Lamminmäki, U., Launis, V., Peltola, V., Xiang-Guo, L., Coffey, E., Meinander, A., Toivola, D. & Zhang, H.
01/07/20 → 30/04/23
Project: Academy of Finland/Other Research Councils

Cite this

@article{e82646d49bcf4d3cbe9236b91dd422f7,

title = "Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy",

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.",

author = "Jiahui Zhang and Cheng Ji and Hongbo Zhang and Hui Shi and Fei Mao and Hui Qian and Wenrong Xu and Dongqing Wang and Jianming Pan and Xinjian Fang and Santos, {H{\'e}lder A.} and Xu Zhang",

year = "2022",

month = jan,

day = "14",

doi = "10.1126/sciadv.abj8207",

language = "English",

volume = "8",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American association for the advancement of science",

number = "2",

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TY - JOUR

T1 - Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy

AU - Zhang, Jiahui

AU - Ji, Cheng

AU - Zhang, Hongbo

AU - Shi, Hui

AU - Mao, Fei

AU - Qian, Hui

AU - Xu, Wenrong

AU - Wang, Dongqing

AU - Pan, Jianming

AU - Fang, Xinjian

AU - Santos, Hélder A.

AU - Zhang, Xu

PY - 2022/1/14

Y1 - 2022/1/14

N2 - 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.

AB - 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.

U2 - 10.1126/sciadv.abj8207

DO - 10.1126/sciadv.abj8207

M3 - Article

SN - 2375-2548

VL - 8

JO - Science Advances

JF - Science Advances

IS - 2

M1 - eabj8207

ER -

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

Abstract

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Equipment

Åbo Akademi Functional Printing Center

Projects

FCFH: Finland-China Network in Food and Health Sciences

Targeted delivery of CRISPR/Cas9 for advanced liver cancer therapy through c-Myc knockout

InFLAMES: Innovation Ecosystem based on the Immune System

Cite this