Doxorubicin-loaded bacterial outer-membrane vesicles exert enhanced anti-tumor efficacy in non-small-cell lung cancer

• DOI: 10.1016/j.apsb.2020.02.002
• Publication Date: 2020-02-21T06:45:53Z
• Authors: Kudelaidi Kuerban; Xiwen Gao; Hui Zhang; Jiayang Liu; Mengxue Dong; Lina Wu; Ruihong Ye; Meiqing Feng; Li Ye
• Keywords: MTT assay; Nanocarriers

More efficient drug delivery system and formulation with less adverse effects are needed for the clinical application of broad-spectrum antineoplastic agent doxorubicin (DOX). Here we obtained outer-membrane vesicles (OMVs), a nano-sized proteoliposomes naturally released by Gram-negative bacteria, from attenuated Klebsiella pneumonia prepared doxorubicin-loaded O0MVs (DOX-OMV). Confocal microscopy in vivo distribution study observed that DOX encapsulated OMVs was efficiently transported into NSCLC A549 cells. DOX-OMV resulted intensive cytotoxic cell apoptosis vitro as evident MTT assay, Western blotting flow cytometry due to rapid cellular uptake DOX. In tumor-bearing BALB/c nude mice, presented substantial tumor growth inhibition favorable tolerability pharmacokinetic profile, TUNEL assay H&E staining displayed extensive apoptotic cells necrosis tissues. importantly, OMVs' appropriate immunogenicity enabled recruitment macrophages microenvironment which might synergize their cargo vivo. Our results suggest can not only function biological nanocarriers chemotherapeutic agents but also elicit suitable immune responses, thus having great potential chemoimmunotherapy.