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Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations

BACKGROUND: Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal...

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Autores principales: Ye, Jun, Li, Renjie, Yang, Yanfang, Dong, Wujun, Wang, Yujie, Wang, Hongliang, Sun, Tong, Li, Lin, Shen, Qiqi, Qin, Caiyun, Xu, Xiaoyan, Liao, Hengfeng, Jin, Yiqun, Xia, Xuejun, Liu, Yuling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256566/
https://www.ncbi.nlm.nih.gov/pubmed/34225762
http://dx.doi.org/10.1186/s12951-021-00946-w
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author Ye, Jun
Li, Renjie
Yang, Yanfang
Dong, Wujun
Wang, Yujie
Wang, Hongliang
Sun, Tong
Li, Lin
Shen, Qiqi
Qin, Caiyun
Xu, Xiaoyan
Liao, Hengfeng
Jin, Yiqun
Xia, Xuejun
Liu, Yuling
author_facet Ye, Jun
Li, Renjie
Yang, Yanfang
Dong, Wujun
Wang, Yujie
Wang, Hongliang
Sun, Tong
Li, Lin
Shen, Qiqi
Qin, Caiyun
Xu, Xiaoyan
Liao, Hengfeng
Jin, Yiqun
Xia, Xuejun
Liu, Yuling
author_sort Ye, Jun
collection PubMed
description BACKGROUND: Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential. RESULTS: Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation. CONCLUSIONS: The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy. GRAPHIC ABSTRACT: [Image: see text]
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spelling pubmed-82565662021-07-06 Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations Ye, Jun Li, Renjie Yang, Yanfang Dong, Wujun Wang, Yujie Wang, Hongliang Sun, Tong Li, Lin Shen, Qiqi Qin, Caiyun Xu, Xiaoyan Liao, Hengfeng Jin, Yiqun Xia, Xuejun Liu, Yuling J Nanobiotechnology Research BACKGROUND: Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential. RESULTS: Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation. CONCLUSIONS: The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy. GRAPHIC ABSTRACT: [Image: see text] BioMed Central 2021-07-05 /pmc/articles/PMC8256566/ /pubmed/34225762 http://dx.doi.org/10.1186/s12951-021-00946-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ye, Jun
Li, Renjie
Yang, Yanfang
Dong, Wujun
Wang, Yujie
Wang, Hongliang
Sun, Tong
Li, Lin
Shen, Qiqi
Qin, Caiyun
Xu, Xiaoyan
Liao, Hengfeng
Jin, Yiqun
Xia, Xuejun
Liu, Yuling
Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations
title Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations
title_full Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations
title_fullStr Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations
title_full_unstemmed Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations
title_short Comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations
title_sort comparative colloidal stability, antitumor efficacy, and immunosuppressive effect of commercial paclitaxel nanoformulations
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256566/
https://www.ncbi.nlm.nih.gov/pubmed/34225762
http://dx.doi.org/10.1186/s12951-021-00946-w
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