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

Journal of Nanobiotechnology

Yiqun Jin¹  Yujie Wang¹  Qiqi Shen¹  Caiyun Qin¹  Jun Ye²  Xiaoyan Xu²  Tong Sun²  Lin Li²  Renjie Li²  Yanfang Yang²  Hongliang Wang²  Hengfeng Liao²  Xuejun Xia²  Yuling Liu²  Wujun Dong² 

[1]Beijing Wehand-Bio Pharmaceutical Co. Ltd., 102600, Beijing, People’s Republic of China

[2]State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan Street, 100050, Beijing, People’s Republic of China

[3]Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 100050, Beijing, People’s Republic of China

关键词: Paclitaxel;    Nanoparticle;    Liposome;    Emulsion;    Stability;    Immunosuppression;   

DOI  :  10.1186/s12951-021-00946-w

来源: Springer

【 摘 要 】

BackgroundStandard 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.ResultsCompared 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.ConclusionsThe 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

【 授权许可】

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