Paclitaxel derivative-based liposomal nanoplatform for potentiated chemo-immunotherapy.

Journal of controlled release : official journal of the Controlled Release Society 2022 Jan

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The combination of chemotherapy with the immune checkpoint blockade (ICB) therapy is bringing a tremendous hope in the treatment of malignant tumors. However, the treatment efficacy of the existing chemo-immunotherapy is not satisfactory due to the high cost and immunogenicity of ICB antibodies, low response rate to ICB, off-target toxicity of therapeutic agents, and low drug co-delivery efficacy. Therefore, a high-efficient nanosystem combining the delivery of chemotherapeutics with small molecule ICB inhibitors may be promising for an efficient cancer therapy. Herein, a novel reactive oxygen species (ROS)-activated liposome nanoplatform was constructed by the loading of a ROS-sensitive paclitaxel derivative (PSN) into liposomes to overcome the difficulties on delivering paclitaxel mostly represented by premature drug release and a low amount accumulated into the tumor. The innovative liposomal nanosystem was rationally designed by a remote loading of BMS-202 (a small molecule PD-1/PD-L1 inhibitor) and PSN into the liposomes for a ROS-sensitive paclitaxel release and sustained BMS-202 release. The co-loaded liposomes resulted in a high co-loading ability and improved pharmacokinetic properties. An orthotopic 4 T1 breast cancer model was used to evaluate the efficiency of our nanoplatform in vivo, resulting in a superior antitumor activity. The antitumor immunity was activated by paclitaxel-mediated immunogenic cell death, while BMS-202 continuously blocked PD-L1 which could be up-regulated by paclitaxel in tumors to increase the response to ICB and further recover the host immune surveillance. These results revealed that this dual-delivery liposome might provide a promising strategy for a high-efficient chemo-immunotherapy, exhibiting a great potential for clinical translation. Copyright © 2021. Published by Elsevier B.V.

Citation

Yingli Wang, Jiang Yu, Dan Li, Liwen Zhao, Bingjun Sun, Jiamei Wang, Zhenjie Wang, Shuang Zhou, Menglin Wang, Yinxian Yang, Hongzhuo Liu, Haotian Zhang, Qingzhi Lv, Qikun Jiang, Zhonggui He, Yongjun Wang. Paclitaxel derivative-based liposomal nanoplatform for potentiated chemo-immunotherapy. Journal of controlled release : official journal of the Controlled Release Society. 2022 Jan;341:812-827