Intracellular redox induced drug release in cancerous and mesenchymal stem cells

•Redox-responsive microcapsules with covalently bonded drug were prepared.•Drug-conjugated capsules showed high uptake efficacy against cancerous cells.•The cytotoxicity of cancer cells is much higher compared to human normal cells. [Display omitted] Intracellular redox induced release of doxorubici...

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Bibliographic Details
Published in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2016-11, Vol.147, p.450-458
Main Authors: Timin, Alexander S., Lepik, Kirill V., Muslimov, Albert R., Gorin, Dmitry A., Afanasyev, Boris V., Sukhorukov, Gleb B.
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - pharmacology
Biodegradation
Bonding
Cancer
Cancer therapy
Cell Survival - drug effects
Cells, Cultured
Crosslinking
Disulfides
Doxorubicin - pharmacology
Drug delivery systems
Drug Liberation
Drugs
Glutathione
HeLa Cells
Humans
Mesenchymal stem cells
Mesenchymal Stromal Cells - drug effects
Nanoparticles - chemistry
Oxidation-Reduction
Polyelectrolyte capsules
Stem cells
Therapy
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Summary:•Redox-responsive microcapsules with covalently bonded drug were prepared.•Drug-conjugated capsules showed high uptake efficacy against cancerous cells.•The cytotoxicity of cancer cells is much higher compared to human normal cells. [Display omitted] Intracellular redox induced release of doxorubicin from biodegradable capsule in cancerous cell. In this report, we investigated intracellular redox induced drug release in cancerous cells and human mesenchymal stem cells (MSCs) as an example of healthy cells using redox-responsive microcapsules with covalently bonded anti-cancer drug (doxorubicin) via the amine-reactive cross-linker, 3,3′-dithiobis(sulfosuccinimidyl propionate) containing disulfide bond. Such rationally designed capsules with incorporated redox-sensitive cross-linker are capable of controllable Dox release in the presence of glutathione (GSH) due to a thiol-cleavable disulfide bonds. The treatment of human MSCs and human cervical cancer cell line (HeLa) with Dox-conjugated capsules showed that the Dox release was observed only when capsules incubated with HeLa cells which can be induced by high GSH level in cancerous (HeLa) cells. Moreover, the results of cell viability indicated that Dox-conjugated capsules are more effective when inducing cell death of HeLa than free Dox improving the anti-tumor efficacy of chemotherapeutic drug and simultaneously they possess lower cytotoxicity against MSCs compared to cancerous cells. Such properties are important in design of smart drug carriers for efficient cancer therapy.
ISSN:0927-7765
1873-4367
DOI:10.1016/j.colsurfb.2016.08.034