M1 macrophage-derived exosomes synergistically enhance the anti- bladder cancer effect of gemcitabine
Open accessAbstract
Gemcitabine (GEM) is one of the first choice drugs for treating bladder cancer. In this study, we loaded M1 macrophage-derived exosomes (M1-Exo) with GEM by ultrasonication technique to derive an M1-Exo-GEM drug delivery system, and then explored its effects on bladder cancer. After inducing M1 polarization of macrophages in vitro, ultracentrifugation was performed to obtain M1-Exo, followed by construction of M1-Exo-GEM via ultrasonication technique. Mouse bladder cancer MB49 cells were chosen for study. CCK-8, PI staining and flow cytometry (FCM) assays were employed to assess the cell viability and apoptosis level. Inflammatory cytokines were detected by ELISA, while the protein expressions of Bcl-2, Bax and Caspase-3 were examined through Western-Blotting. After injecting M1-Exo-GEM into the tumor-bearing mouse model, the pathological changes were observed by H&E staining, the cancer cell damage was detected by TUNEL staining, and the apoptosis pathway activation was analyzed through immunohistochemical (IHC) staining and protein expression assays for Caspase-3 and Bax. Our results showed that M1-Exo and GEM had cytotoxic effects on MB49 cells, which increased the apoptosis level and the inflammatory cytokine expressions. Compared to M1-Exo and GEM, M1-Exo-GEM was significantly more cytotoxic to MB49 cells while markedly up-regulating the expressions of inflammatory cytokines. In the tumor-bearing mouse model, M1-Exo-GEM significantly inhibited tumor growth and damaged tumor cells, which outperformed GEM. Meanwhile, it also increased the tissue levels of inflammatory cytokines. This study finds that the drug delivery system composed of M1-Exo and GEM can act synergistically with GEM to exert cytotoxicity and induce inflammatory damage of bladder cancer cells.
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M1-Exo-GEM had significantly up-regulated expression of inflammatory cytokines and stronger cytotoxic effect on cancer cells compared with M1-Exo and GEM.
“Compared with M1-Exo and GEM, M1-Exo-GEM had significantly up-regulated the expression of inflammatory cytokines and stronger cytotoxic effect on cancer cells [100].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [100]
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The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System
Li, T., Li, X., Han, G., Liang, M., Yang, Z., Zhang, C., Huang, S., Tai, S., & Yu, S. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics15010021 · Cited by 110 · see citing works
- Authors
- Tang, Z., Tang, C., Sun, C., Ying, X., & Shen, R.
- Affiliations
- Jiaxing University (CN)
- Corresponding author
- Shen, Ruilin
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2022-08-03
- Volume
- 14
- Issue
- 18
- Pages
- 7364-7377
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC9550252
- OpenAlex
- W4289594738
- Cited by
- 26
- References
- 25
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 11 · 2023: 8 · 2022: 1
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- gemcitabine, bladder cancer, exosome-based drug delivery, macrophage polarization, apoptosis, inflammatory cytokines, tumor growth inhibition, drug synergy, MB49 cells, Bax, caspase-3
- MeSH terms
- Gemcitabine, Animals, Antineoplastic Agents, Urinary Bladder Neoplasms, Deoxycytidine, Disease Models, Animal, Macrophages, Cytokines, bcl-2-Associated X Protein, Mice, Caspase 3, Exosomes
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