title: Intracellular redox induced drug release in cancerous and mesenchymal stem cells.
abstract: 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.
authors: RASA center in Tomsk, Tomsk Polytechnic University, pros. Lenina, 30, Tomsk, Russian Federation. Electronic address: a_timin@mail.ru.
authors: Alexander S
authors: AS
authors: Timin
authors: First I. P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str., 6/8, Saint-Petersburg, Russian Federation.
authors: Kirill V
authors: KV
authors: Lepik
authors: First I. P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str., 6/8, Saint-Petersburg, Russian Federation.
authors: Albert R
authors: AR
authors: Muslimov
authors: RASA center in Tomsk, Tomsk Polytechnic University, pros. Lenina, 30, Tomsk, Russian Federation; Saratov State University, Astrakhanskaya Street 83, Saratov 410012, Russian Federation.
authors: Dmitry A
authors: DA
authors: Gorin
authors: First I. P. Pavlov State Medical University of St. Petersburg, Lev Tolstoy str., 6/8, Saint-Petersburg, Russian Federation.
authors: Boris V
authors: BV
authors: Afanasyev
authors: RASA center in Tomsk, Tomsk Polytechnic University, pros. Lenina, 30, Tomsk, Russian Federation; RASA center in St.Petersburg, Peter The Great St.Petersburg Polytechnic University, St.Petersburg, Russian Federation; School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, United Kingdom.
authors: Gleb B
authors: GB
authors: Sukhorukov
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D065546:Drug Liberation; D006367:HeLa Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: Biodegradation; Cancer therapy; Glutathione; Mesenchymal stem cells; Polyelectrolyte capsules