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Bacterial Outer Membrane Vesicles Loaded with Perhexiline Suppress Tumor Development by Regulating Tumor-Associated
Shoujin Jiang1, Wei Fu1, Sijia Wang1
1School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
Abstract:
Tumor-associated macrophages (TAMs) promote tumor development and metastasis and are categorized into M1-like macrophages, suppressing tumor cells, and M2-like macrophages. M2-like macrophages, occupying a major role in TAMs, can be repolarized into anti-tumoral phenotypes. In this study, outer membrane vesicles (OMVs) secreted by Escherichia coli Nissle 1917 carry perhexiline (OMV@Perhx) to explore the influence of OMVs and perhexiline on TAM repolarization. OMV@Perhx was internalized by macrophages and regulated the phenotype of TAMs from M2-like to M1-like efficiently to increase the level of tumor suppressor accordingly. Re-polarized macrophages promoted apoptosis and inhibited the mobility of tumor, cells including invasion and migration. The results indicate that OMVs improve the efficacy of perhexiline and also represent a promising natural immunomodulator. Combining OMVs with perhexiline treatments shows powerfully synergistic anti-tumor effects through co-culturing with re-polarized macrophages. This work is promising to exploit the extensive applications of OMVs and chemical drugs, therefore developing a meaningful drug carrier and immunomodulator as well as expanding the purposes of traditional chemical drugs.
Insights
Outer membrane vesicles (OMVs) carrying perhexiline reprogram tumor-associated macrophages (TAMs) from M2-like to M1-like phenotypes. This OMV@Perhx strategy enhances anti-tumor activity by promoting apoptosis and inhibiting tumor cell migration.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Tumor-associated macrophages (TAMs) are crucial for tumor progression and metastasis.
- TAMs, predominantly M2-like, can be reprogrammed into anti-tumoral M1-like phenotypes.
- Outer membrane vesicles (OMVs) offer potential as drug carriers and immunomodulators.
Purpose of the Study:
- To investigate the efficacy of OMVs from Escherichia coli Nissle 1917 loaded with perhexiline (OMV@Perhx) in repolarizing TAMs.
- To evaluate the anti-tumor effects of OMV@Perhx-mediated TAM repolarization.
Main Methods:
- Macrophages were treated with OMV@Perhx to induce TAM repolarization.
- The impact of repolarized macrophages on tumor cell apoptosis, invasion, and migration was assessed.
- Synergistic anti-tumor effects of combined OMVs and perhexiline were analyzed.
Main Results:
- OMV@Perhx effectively repolarized M2-like TAMs to M1-like phenotypes.
- Repolarized macrophages significantly promoted tumor cell apoptosis.
- Tumor cell invasion and migration were inhibited by the repolarized macrophages.
Conclusions:
- OMVs enhance perhexiline efficacy, acting as a novel drug carrier and immunomodulator.
- Combined OMV and perhexiline treatment exhibits potent synergistic anti-tumor effects.
- This approach holds promise for developing new cancer therapies by leveraging OMVs and chemical drugs.
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