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Redox‐Triggered Nanomedicine via Lymphatic Delivery: Inhibition of Melanoma Growth by Ferroptosis Enhancement and a Pt(IV)‐Prodrug Chemoimmunotherapy Approach

Marc Bilbao Asensio, Ane Ruiz‐de‐Angulo, Amaia Garaikoetxea Arguinzoniz, James Cronin Orcid Logo, Jordi Llop, Aintzane Zabaleta, Saul Michue-Seijas, Dominika Sosnowska, James N. Arnold, Juan Mareque-Rivas Orcid Logo

Advanced Therapeutics, Volume: 6, Issue: 2, Start page: 2200179

Swansea University Authors: Marc Bilbao Asensio, James Cronin Orcid Logo, Saul Michue-Seijas, Juan Mareque-Rivas Orcid Logo

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DOI (Published version): 10.1002/adtp.202200179

Abstract

The efficacy of therapies is often hampered by limited tumor drug accumulation achieved through their intravenous administration, and by the lack of selectivity in targeting and killing cancer cells. Amplification of tumor redox stress and ferroptotic cell death to achieve selective killing of cance...

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Published in: Advanced Therapeutics
ISSN: 2366-3987 2366-3987
Published: Wiley 2022
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa61668
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Abstract: The efficacy of therapies is often hampered by limited tumor drug accumulation achieved through their intravenous administration, and by the lack of selectivity in targeting and killing cancer cells. Amplification of tumor redox stress and ferroptotic cell death to achieve selective killing of cancer cells using iron-containing agents has attracted considerable interest. However, these agents need high doses and multiple injection regimens and had limited success in the treatment of cancers such as melanoma. Melanoma often metastasizes via lymphatic vessels, where the metastasizing cells experience less redox stress and are protected from ferroptosis. Here we show that phospholipid-modified Pt(IV) prodrug-loaded iron oxide nanoparticle (IONP)-filled micelles (mIONP-PL-Pt(IV)), which integrate redox reactivity and iron-enabled catalytic therapeutic features with effective nanoparticle-assisted lymphatic delivery, provide significantly enhanced suppression of melanoma tumor growth compared to cisplatin-based chemotherapy and iron oxide nanoparticle treatments. Peroxidase-like activity, redox-triggered release of cisplatin and reactivity with hydrogen peroxide and ascorbic acid are contributors towards the induction of a combined ferroptosis-based and cisplatin anti-melanoma treatment. Treatment with mIONP-PL-Pt(IV) provided significant tumor control using cumulative treatment doses 10 to 100-fold lower than reported in intravenously administered treatments. This work demonstrates the potential of enhancing chemotherapeutic and iron-based catalytic nanomedicine efficacy exploiting nanoparticle-enabled lymphatic trafficking.
Keywords: Ferroptosis; Platinum(IV) prodrugs; Iron oxide nanoparticles; ROS, Lymphatic system; Drug delivery; Melanoma treatment
College: Faculty of Science and Engineering
Funders: Medical Research Council (GrantNumber(s): MC_PC_19053) Engineering and Physical Sciences Research Council (GrantNumber(s): 2105067) Cancer Research UK (GrantNumber(s): DCRPGF\100009) Cancer Research Institute (GrantNumber(s): Wade F.B. Thompson CLIP grant (CRI3645))
Issue: 2
Start Page: 2200179