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Self-assembled hyaluronic acid nanomicelle for enhanced cascade cancer chemotherapy via self-sensitized ferroptosis.
- Source :
-
Carbohydrate polymers [Carbohydr Polym] 2024 Nov 01; Vol. 343, pp. 122489. Date of Electronic Publication: 2024 Jul 14. - Publication Year :
- 2024
-
Abstract
- The clinical utility of chemotherapy is often compromised by its limited efficacy and significant side effects. Addressing these concerns, we have developed a self-assembled nanomicelle, namely SANTA FE OXA, which consists of hyaluronic acid (HA) conjugated with ferrocene methanol (FC), oxaliplatin prodrug (OXA(IV)) and ethylene glycol-coupled linoleic acid (EG-LA). Targeted delivery is achieved by HA binding to the CD44 receptors that are overexpressed on tumor cells, facilitating drug uptake. Once internalized, hyaluronidase (HAase) catalyzes the digestion of the SANTA FE OXA, releasing FC and reducing OXA(IV) into an active form. The active oxaliplatin (OXA) induces DNA damage and increases intracellular hydrogen peroxide (H <subscript>2</subscript> O <subscript>2</subscript> ) levels via cascade reactions. Simultaneously, FC disrupts the redox balance within tumor cells, inducing ferroptosis. Both in vivo and in vitro experiments confirmed that SANTA FE OXA inhibited tumor growth by combining cascade chemotherapy and self-sensitized ferroptosis, achieving a tumor inhibition rate of up to 76.61 %. Moreover, this SANTA FE OXA significantly mitigates the systemic toxicity commonly associated with platinum-based chemotherapeutics. Our findings represent a compelling advancement in nanomedicine for enhanced cascade cancer therapy.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Subjects :
- Humans
Animals
Mice
Cell Line, Tumor
Metallocenes chemistry
Metallocenes pharmacology
Prodrugs pharmacology
Prodrugs chemistry
Linoleic Acid chemistry
Linoleic Acid pharmacology
Mice, Inbred BALB C
Female
Mice, Nude
Hydrogen Peroxide chemistry
Hydrogen Peroxide pharmacology
Neoplasms drug therapy
Hyaluronic Acid chemistry
Hyaluronic Acid pharmacology
Ferroptosis drug effects
Oxaliplatin pharmacology
Oxaliplatin chemistry
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
Micelles
Ferrous Compounds chemistry
Ferrous Compounds pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-1344
- Volume :
- 343
- Database :
- MEDLINE
- Journal :
- Carbohydrate polymers
- Publication Type :
- Academic Journal
- Accession number :
- 39174141
- Full Text :
- https://doi.org/10.1016/j.carbpol.2024.122489