Intracellular redox induced drug release in cancerous and mesenchymal stem cells

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 147; pp. 450 - 458
• Main Authors: Timin, Alexander S., Lepik, Kirill V., Muslimov, Albert R., Gorin, Dmitry A., Afanasyev, Boris V., Sukhorukov, Gleb B.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2016
• 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; Polyelectrolyte capsules; Biodegradation; Cancer therapy; Glutathione; Mesenchymal stem cells
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2016.08.034

•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.