Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

Dandan Ling,Xueli Jia, Ke Wang, Qiucheng Yan,Bochuan Yuan,Lina Du, Miao Li,Yiguang Jin

ACTA PHARMACEUTICA SINICA B(2024)

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摘要
Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane -coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer -by -layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4 thorn /CD8a thorn T cells in the spleen and the TNF-a, IFN-g, and IL -4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY -NCND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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关键词
Apoptosis,Bacterial ghost,Cancer cell membrane,Immune stimulation,Liposome,Lung targeting,Metastatic lung cancer,Paclitaxel
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