TY - JOUR
T1 - Engineered Exosomes Carrying miR-588 for Treatment of Triple Negative Breast Cancer Through Remodeling the Immunosuppressive Microenvironment
AU - Zhang, Zhengjia
AU - Luo, Xinyi
AU - Xue, Xiaoxia
AU - Pang, Mingshi
AU - Wang, Xiangpeng
AU - Yu, Liuchunyang
AU - Qian, Jinxiu
AU - Li, Xiaoyu
AU - Tian, Meng
AU - Lu, Aiping
AU - Lu, Cheng
AU - Liu, Yuanyan
N1 - This work was supported by The National Natural Science Foundation of China (82074269) Youth Qihuang Scholar of National Administration of Traditional Chinese Medicine (2020). A special thanks for the long-term subsidy mechanism from the Ministry of Finance and the Ministry of Education of PRC (People’s Republic of China) for Beijing University of Chinese Medicine and China Academy of Chinese Medical Sciences.
Publisher Copyright:
© 2024 Zhang et al.
PY - 2024/1/23
Y1 - 2024/1/23
N2 - Background: The morbidity and mortality of triple-negative breast cancer (TNBC) are still high, causing a heavy medical burden. CCL5, as a chemokine, can be involved in altering the composition of the tumor microenvironment (TME) as well as the immunosuppressive degree, and has become a very promising target for the treatment of TNBC. Dysregulation of microRNAs (miRNAs) in tumor tissues is closely related to tumor progression, and its utilization can be used to achieve therapeutic purposes. Engineered exosomes can avoid the shortcomings of miRNAs and also enhance their targeting and anti-tumor effects through engineering. Therefore, we aimed to create a cRGD-modified exosome for targeted delivery of miR-588 and to investigate its effect in remodeling immunosuppressive TME by anchoring CCL5 in TNBC.Methods: In this study, we loaded miR-588 into exosomes using electroporation and modified it with cRGD using post insertion to obtain cRGD-Exos/miR-588. Transmission electron microscopy (TEM), nanoparticle tracking assay technique (NTA), Western Blots, qPCR, and flow cytometry were applied for its characterization. CCK-8, qPCR and enzyme-linked immunosorbent assay (ELISA), in vivo fluorescence imaging system, immunohistochemistry and H&E staining were used to explore the efficacy as well as the mechanism at the cellular level as well as in subcutaneous graft-tumor nude mouse model.Results: The cRGD-Exos/miR-588 was successfully constructed and had strong TNBC tumor targeting in vitro and in vivo. Meanwhile, it has significant efficacy on TME components affected by CCL5 and the degree of immunosuppression, which can effectively control TNBC with good safety.Conclusion: In this experiment, cRGD-Exos/miR-588 was prepared to remodel immunosuppressive TME by anchoring CCL5, which is affected by the vicious cycle of immune escape. Overall, cRGD-Exos/miR-588 explored the feasibility of targeting TME for the TNBC treatment, and provided a competitive delivery system for the engineered exosomes to deliver miRNAs for antitumor therapy drug.
AB - Background: The morbidity and mortality of triple-negative breast cancer (TNBC) are still high, causing a heavy medical burden. CCL5, as a chemokine, can be involved in altering the composition of the tumor microenvironment (TME) as well as the immunosuppressive degree, and has become a very promising target for the treatment of TNBC. Dysregulation of microRNAs (miRNAs) in tumor tissues is closely related to tumor progression, and its utilization can be used to achieve therapeutic purposes. Engineered exosomes can avoid the shortcomings of miRNAs and also enhance their targeting and anti-tumor effects through engineering. Therefore, we aimed to create a cRGD-modified exosome for targeted delivery of miR-588 and to investigate its effect in remodeling immunosuppressive TME by anchoring CCL5 in TNBC.Methods: In this study, we loaded miR-588 into exosomes using electroporation and modified it with cRGD using post insertion to obtain cRGD-Exos/miR-588. Transmission electron microscopy (TEM), nanoparticle tracking assay technique (NTA), Western Blots, qPCR, and flow cytometry were applied for its characterization. CCK-8, qPCR and enzyme-linked immunosorbent assay (ELISA), in vivo fluorescence imaging system, immunohistochemistry and H&E staining were used to explore the efficacy as well as the mechanism at the cellular level as well as in subcutaneous graft-tumor nude mouse model.Results: The cRGD-Exos/miR-588 was successfully constructed and had strong TNBC tumor targeting in vitro and in vivo. Meanwhile, it has significant efficacy on TME components affected by CCL5 and the degree of immunosuppression, which can effectively control TNBC with good safety.Conclusion: In this experiment, cRGD-Exos/miR-588 was prepared to remodel immunosuppressive TME by anchoring CCL5, which is affected by the vicious cycle of immune escape. Overall, cRGD-Exos/miR-588 explored the feasibility of targeting TME for the TNBC treatment, and provided a competitive delivery system for the engineered exosomes to deliver miRNAs for antitumor therapy drug.
KW - CCL5
KW - engineered exosome
KW - miR-588
KW - triple negative breast cancer
KW - tumor environment
UR - http://www.scopus.com/inward/record.url?scp=85183744616&partnerID=8YFLogxK
U2 - 10.2147/IJN.S440619
DO - 10.2147/IJN.S440619
M3 - Journal article
C2 - 38283199
AN - SCOPUS:85183744616
SN - 1176-9114
VL - 19
SP - 743
EP - 758
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
ER -
