The transmission and toxicity of polymer-bound doxorubicin-containing exosomes derived from human adenocarcinoma cells.
Kristýna GunárLenka KotrchováMarcela FilipováTereza KrunclovaAneta DydowiczováRobert PolaEva RandárováTomas EtrychOlga JanouškováPublished in: Nanomedicine (London, England) (2022)
Background: Exosomes are extracellular vesicles with the ability to encapsulate bioactive molecules, such as therapeutics. This study identified a new exosome mediated route of doxorubicin and poly(N-(2-hydroxypropyl)methacrylamide) (pHPMA)-bound doxorubicin trafficking in the tumor mass. Materials & methods: Exosome loading was achieved via incubation of the therapeutics with an adherent human breast adenocarcinoma cell line and its derived spheroids. Exosomes were characterized using HPLC, nanoparticle tracking analysis (NTA) and western blotting. Results: The therapeutics were successfully loaded into exosomes. Spheroids secreted significantly more exosomes than adherent cells and showed decreased viability after treatment with therapeutic-loaded exosomes, which confirmed successful transmission. Conclusion: To the best of our knowledge, this study provides the first evidence of pHPMA-drug conjugate secretion by extracellular vesicles.
Keyphrases
- mesenchymal stem cells
- drug delivery
- stem cells
- cancer therapy
- induced apoptosis
- endothelial cells
- small molecule
- healthcare
- cell cycle arrest
- induced pluripotent stem cells
- oxidative stress
- emergency department
- mass spectrometry
- endoplasmic reticulum stress
- locally advanced
- radiation therapy
- cell death
- adverse drug