Iron chelation cancer therapy using hydrophilic block copolymers conjugated with deferoxamine.
Cancer Sci
; 112(1): 410-421, 2021 Jan.
Article
em En
| MEDLINE
| ID: mdl-32770631
ABSTRACT
Cancer cells have high iron requirements due to their rapid growth and proliferation. Iron depletion using iron chelators has a potential in cancer treatment. Previous studies have demonstrated that deferoxamine (DFO) specifically chelates Fe(III) and exhibited antitumor activity in clinical studies. However, its poor pharmacokinetics has limited the therapeutic potential and practical application. Although polymeric iron chelators have been developed to increase the blood retention, none of previous studies has demonstrated their potential in iron chelation cancer therapy. Here, we developed polymeric DFO by the covalent conjugation of DFO to poly(ethylene glycol)-poly(aspartic acid) (PEG-PAsp) block copolymers. The polymeric DFO exhibited iron-chelating ability comparable with free DFO, thereby arresting cell cycle and inducing apoptosis and antiproliferative activity. After intravenous administration, the polymeric DFO showed marked increase in blood retention and tumor accumulation in subcutaneous tumor models. Consequently, polymeric DFO showed significant suppression of the tumor growth compared with free DFO. This study reveals the first success of the design of polymeric DFO for enhancing iron chelation cancer therapy.
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Base de dados:
MEDLINE
Assunto principal:
Portadores de Fármacos
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Quelantes de Ferro
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Apoptose
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Desferroxamina
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Proliferação de Células
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article