Doxorubicin-loaded bacterial outer-membrane vesicles exert enhanced anti-tumor efficacy in non-small-cell lung cancer.
10.1016/j.apsb.2020.02.002
- Author:
Kudelaidi KUERBAN
1
;
Xiwen GAO
1
;
Hui ZHANG
1
;
Jiayang LIU
1
;
Mengxue DONG
1
;
Lina WU
2
;
Ruihong YE
3
;
Meiqing FENG
1
;
Li YE
1
Author Information
1. Minghang Hospital & Department of Biological Medicines at School of Pharmacy, Fudan University, Shanghai 201100, China.
2. TOF-PET/CT/MR Center, the 4th Affiliated Hospital, Harbin Medical University, Harbin 150028, China.
3. Department of Pharmaceutical Engineering, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430070, China.
- Publication Type:Journal Article
- Keywords:
Anti-tumor efficacy;
Bacterial outer-membrane vesicles;
Chemoimmunotherapy;
Doxorubicin;
Non-small-cell lung cancer
- From:
Acta Pharmaceutica Sinica B
2020;10(8):1534-1548
- CountryChina
- Language:English
-
Abstract:
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 and prepared doxorubicin-loaded O0MVs (DOX-OMV). Confocal microscopy and distribution study observed that DOX encapsulated in OMVs was efficiently transported into NSCLC A549 cells. DOX-OMV resulted in intensive cytotoxic effects and cell apoptosis as evident from MTT assay, Western blotting and flow cytometry due to the rapid cellular uptake of DOX. In A549 tumor-bearing BALB/c nude mice, DOX-OMV presented a substantial tumor growth inhibition with favorable tolerability and pharmacokinetic profile, and TUNEL assay and H&E staining displayed extensive apoptotic cells and necrosis in tumor tissues. More importantly, OMVs' appropriate immunogenicity enabled the recruitment of macrophages in tumor microenvironment which might synergize with their cargo DOX . Our results suggest that OMVs can not only function as biological nanocarriers for chemotherapeutic agents but also elicit suitable immune responses, thus having a great potential for the tumor chemoimmunotherapy.
