Nanosponge for Iron Chelation and Efflux: A Ferroptosis-Inhibiting Approach for Myocardial Infarction Therapy.
Adv Sci (Weinh)
; 11(25): e2305895, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38671590
ABSTRACT
Myocardial infarction (MI), a consequence of coronary artery occlusion, triggers the degradation of ferritin, resulting in elevated levels of free iron in the heart and thereby inducing ferroptosis. Targeting myocardial ferroptosis through the chelation of excess iron has therapeutic potential for MI treatment. However, iron chelation in post ischemic injury areas using conventional iron-specific chelators is hindered by ineffective myocardial intracellular chelation, rapid clearance, and high systemic toxicity. A chitosan-desferrioxamine nanosponge (CDNS) is designed by co-crosslinking chitosan and deferoxamine through noncovalent gelation to address these challenges. This architecture facilitates direct iron chelation regardless of deferoxamine (DFO) release due to its sponge-like porous hydrogel structure. Upon cellular internalization, CDNS can effectively chelate cellular iron and facilitate the efflux of captured iron, thereby inhibiting ferroptosis and associated oxidative stress and lipid peroxidation. In MI mouse models, myocardial injection of CDNS promotes sustainable retention and the suppression of ferroptosis in the infarcted heart. This intervention improves cardiac function and alleviates adverse cardiac remodeling post-MI, leading to decreased oxidative stress and the promotion of angiogenesis due to ferroptosis inhibition by CDNS in the infarcted heart. This study reveals a nanosponge-based nanomedicine targeting myocardial ferroptosis with efficient iron chelation and efflux, offering a promising MI treatment.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Iron Chelating Agents
/
Disease Models, Animal
/
Ferroptosis
/
Myocardial Infarction
Limits:
Animals
Language:
En
Journal:
Adv Sci (Weinh)
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Germany