Targeted niosomes protect the heart from doxorubicin-induced injury: evidence from oxidative stress, pyroptosis, and apoptosis pathways.

Authors

Singaravel Vijayapoopathi, Kalaiyarasi Kasirajan, Malathi Sampath, Bhuvarahamurthy Venugopal

Published in

3 Biotech. Volume 16. Issue 9. Pages 369. Epub Aug 06, 2026.

Abstract

Doxorubicin (DOX) is a frontline chemotherapeutic agent whose clinical utility is significantly limited by dose-dependent and often irreversible cardiotoxicity. Niosomal drug delivery systems, owing to their biocompatibility and tumour-targeting potential, often a promising strategy to enhance therapeutic efficacy while mitigating systemic toxicity. In this study, we developed epidermal growth factor receptor (EGFR)-targeted, centuximab-conjugated niosomes co-loaded with DOX and vitexin (NIODVC) and evaluated their cardioprotective efficacy in 4T1 breast tumor-bearing BALB/c mice. Non-targeted niosomes (NIODV) facilitated tumor-specific delivery but were associated with cardiac injury. In contrast, centuximab-modified NIODVC improved formulation stability, enhanced therapeutic effectiveness, and reduced off-target cardiotoxicity. Cardioprotection was supported by normalization of hematological indices, restoration of serum biochemical and oxidative stress markers, preservation of antioxidant competence, and maintenance of myocardial histoarchitecture. Molecular analysis demonstrated upregulation of antioxidant genes (Nrf2, Ho-1, Nqo1, Sod1, Sod2) and suppression of the pro-oxidant gene p67phox. NIODVC also reduced expression of pyroptosis-related mediators (Nlrp3, Caspase-1, Gsdmd, Il-1β, Il-18) and favorably modulated apoptotic balance by increasing Bcl2 and reducing Bax expression relative to NIODV. Notably, intratumoural administration provided grater cardioprotection than intravenous delivery. Taken together, these findings suggest that NIODVC represents a multifunctional nanocarrier capable of enhancing anticancer efficacy while mitigating DOX-induced cardiac injury, Supports its potential for safer breast cancer chemotherapy.

PMID:
42568604
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.