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EnglishSeveral reports indicate that chemo-resistant cancer cells become highly adapted to intrinsic oxidative stress by up-regulating their antioxidant systems, which causes an increase of intracellular GSH content. Doxorubicin is one of the most widely used drugs for tumor treatment, able to kill cancer cells through several mechanisms. However, doxorubicin use is limited by its toxicity and cancer resistance. Therefore, new therapeutic strategies able to reduce doses and to overcome chemo-resistance are needed. A new class of glutathione-responsive cyclodextrin nanosponges (GSH-NS), is able to release anticancer drugs preferentially in cells having high GSH content. Doxorubicin-loaded GSH-NS, in the cancer cells with high GSH content, inhibited clonogenic growth, cell viability, topoisomerase II activity and induced DNA damage with higher effectiveness than free drug. Moreover, GSH-NS reduced the development of human tumor in xenograft models more than free drug. These characteristics indicate that GSH-NS can be a suitable drug delivery carrier for future applications in cancer therapy.
| Titolo: | GSH-targeted nanosponges increase doxorubicin-induced toxicity "in vitro" and "in vivo" in cancer cells with high antioxidant defenses | |
| Autori Riconosciuti: | ||
| Autori: | Daga, Martina; Ullio, Chiara; Argenziano, Monica; Dianzani, Chiara; Cavalli, Roberta; Trotta, Francesco; Ferretti, Carlo; Zara, Gian Paolo; Gigliotti, Casimiro L.; Ciamporcero, Eric S.; Pettazzoni, Piergiorgio; Corti, Denise; Pizzimenti, Stefania; Barrera, Giuseppina | |
| Data di pubblicazione: | 2016 | |
| Abstract: | Several reports indicate that chemo-resistant cancer cells become highly adapted to intrinsic oxidative stress by up-regulating their antioxidant systems, which causes an increase of intracellular GSH content. Doxorubicin is one of the most widely used drugs for tumor treatment, able to kill cancer cells through several mechanisms. However, doxorubicin use is limited by its toxicity and cancer resistance. Therefore, new therapeutic strategies able to reduce doses and to overcome chemo-resistance are needed. A new class of glutathione-responsive cyclodextrin nanosponges (GSH-NS), is able to release anticancer drugs preferentially in cells having high GSH content. Doxorubicin-loaded GSH-NS, in the cancer cells with high GSH content, inhibited clonogenic growth, cell viability, topoisomerase II activity and induced DNA damage with higher effectiveness than free drug. Moreover, GSH-NS reduced the development of human tumor in xenograft models more than free drug. These characteristics indicate that GSH-NS can be a suitable drug delivery carrier for future applications in cancer therapy. | |
| Volume: | 97 | |
| Pagina iniziale: | 24 | |
| Pagina finale: | 37 | |
| Digital Object Identifier (DOI): | 10.1016/j.freeradbiomed.2016.05.009 | |
| URL: | www.elsevier.com/locate/freeradbiomed | |
| Parole Chiave: | Doxorubicin; GSH-targeted nanosponges; Prostate and colon cancer cells; Toxic effects; Biochemistry; Physiology (medical) | |
| Rivista: | FREE RADICAL BIOLOGY & MEDICINE | |
| Appare nelle tipologie: | 03A-Articolo su Rivista |
File in questo prodotto:
| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| 2016 FRBM GSH-NS.pdf | PDF EDITORIALE | Utenti riconosciuti Richiedi una copia | ||
| 2016 FREE RAD BIOL MED GSH-NS_POST PRINT_4aperto.pdf | POSTPRINT (VERSIONE FINALE DELL’AUTORE) | Open Access Visualizza/Apri |
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