Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapy

Journal of Nanobiotechnology

Research

Feng Guo¹  Qiaofeng Jin²  Tang Gao²  Jing Wang²  Boping Jing²  Yuji Xie²  Yuman Li²  Yihan Chen²  He Li²  Li Zhang³  Mingxing Xie³  Rui An⁴  Yu Gao⁴ 

[1]Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China

[2]Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China

[3]Clinical Research Center for Medical Imaging in Hubei Province, 1277 Jiefang Ave, 430022, Wuhan, Hubei, China

[4]Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China

[5]Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China

[6]Clinical Research Center for Medical Imaging in Hubei Province, 1277 Jiefang Ave, 430022, Wuhan, Hubei, China

[7]Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China

[8]Shenzhen Huazhong University of Science and Technology Research Institute, 518607, Shenzhen, China

[9]Hubei Key Laboratory of Molecular Imaging, 430022, Wuhan, China

[10]Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China

关键词: Cancer stem cells;    Napabucasin;    Tumor-derived microparticles;    PET/CT imaging;    JAK-STAT pathway;   

DOI  :  10.1186/s12951-023-01792-8

 received in 2022-08-30, accepted in 2023-01-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCancer stem cells (CSCs) are crucial for the growth, metastasis, drug resistance, recurrence, and spread of tumors. Napabucasin (NAP) could effectively inhibit CSC, but its mechanism has not been fully explained. Additionally, NAP also has the drawbacks of poor water solubility and low utilization. Therefore, this study not only elaborated the new mechanism of NAP inhibiting CSCs, but also built NAP-loaded nanoprobes using apoptotic tumor-derived microparticles (TMPs) as carriers to combine diagnose and treat of colon cancer and lessen the adverse effects of NAP.ResultsThe study discovered a new mechanism for NAP inhibiting tumors. NAP, in addition to inhibiting STAT3, may also inhibit STAT1, thereby inhibiting the expression of CD44, and the stemness of colon cancer. N3-TMPs@NAP was successfully synthesized, and it possessed a lipid bilayer with a particle size of 220.13 ± 4.52 nm, as well as strong tumor binding ability and anti-tumor effect in vitro. In static PET/CT imaging studies, the tumor was clearly visible and showed higher uptake after N3-TMPs@NAP injection than after oral administration. The average tumor volume and weight of the N3-TMPs@NAP group on day 14 of the treatment studies were computed to be 270.55 ± 107.59 mm3 and 0.30 ± 0.12 g, respectively. These values were significantly lower than those of the other groups. Additionally, N3-TMPs@NAP might prevent colon cancer from spreading to the liver. Furthermore, due to TMPs’ stimulation of innate immunity, N3-TMPs@NAP might stimulate anti-tumor.ConclusionsAs a combined diagnostic and therapeutic nanoprobe, N3-TMPs@NAP could successfully conduct PET/CT imaging, suppress CSCs, and synergistically stimulate anticancer immune responses. Additionally, this nanoprobe might someday be employed in clinical situations because TMPs for it can be produced from human tissue and NAP has FDA approval.

【 授权许可】

CC BY   
© The Author(s) 2023

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