Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapy
Abstract Background Cancer 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 a...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-02-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-023-01792-8 |
| _version_ | 1811171580291579904 |
|---|---|
| author | Boping Jing Feng Guo Rui An Yu Gao Yuman Li Yuji Xie Jing Wang Yihan Chen He Li Tang Gao Qiaofeng Jin Li Zhang Mingxing Xie |
| author_facet | Boping Jing Feng Guo Rui An Yu Gao Yuman Li Yuji Xie Jing Wang Yihan Chen He Li Tang Gao Qiaofeng Jin Li Zhang Mingxing Xie |
| author_sort | Boping Jing |
| collection | DOAJ |
| description | Abstract Background Cancer 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. Results The 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. Conclusions As 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. |
| first_indexed | 2024-04-10T17:16:25Z |
| format | Article |
| id | doaj.art-a0276e59f74a4123ba568a021a76a40d |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-10T17:16:25Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-a0276e59f74a4123ba568a021a76a40d2023-02-05T12:22:49ZengBMCJournal of Nanobiotechnology1477-31552023-02-0121111910.1186/s12951-023-01792-8Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapyBoping Jing0Feng Guo1Rui An2Yu Gao3Yuman Li4Yuji Xie5Jing Wang6Yihan Chen7He Li8Tang Gao9Qiaofeng Jin10Li Zhang11Mingxing Xie12Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyHubei Key Laboratory of Molecular ImagingHubei Key Laboratory of Molecular ImagingDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Cancer 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. Results The 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. Conclusions As 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.https://doi.org/10.1186/s12951-023-01792-8Cancer stem cellsNapabucasinTumor-derived microparticlesPET/CT imagingJAK-STAT pathway |
| spellingShingle | Boping Jing Feng Guo Rui An Yu Gao Yuman Li Yuji Xie Jing Wang Yihan Chen He Li Tang Gao Qiaofeng Jin Li Zhang Mingxing Xie Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapy Journal of Nanobiotechnology Cancer stem cells Napabucasin Tumor-derived microparticles PET/CT imaging JAK-STAT pathway |
| title | Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapy |
| title_full | Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapy |
| title_fullStr | Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapy |
| title_full_unstemmed | Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapy |
| title_short | Apoptotic tumor cell-derived microparticles loading Napabucasin inhibit CSCs and synergistic immune therapy |
| title_sort | apoptotic tumor cell derived microparticles loading napabucasin inhibit cscs and synergistic immune therapy |
| topic | Cancer stem cells Napabucasin Tumor-derived microparticles PET/CT imaging JAK-STAT pathway |
| url | https://doi.org/10.1186/s12951-023-01792-8 |
| work_keys_str_mv | AT bopingjing apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT fengguo apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT ruian apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT yugao apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT yumanli apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT yujixie apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT jingwang apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT yihanchen apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT heli apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT tanggao apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT qiaofengjin apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT lizhang apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy AT mingxingxie apoptotictumorcellderivedmicroparticlesloadingnapabucasininhibitcscsandsynergisticimmunetherapy |