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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
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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. 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spelling v2 61668 2022-10-27 Redox‐Triggered Nanomedicine via Lymphatic Delivery: Inhibition of Melanoma Growth by Ferroptosis Enhancement and a Pt(IV)‐Prodrug Chemoimmunotherapy Approach ae3834a12e3216058248bf0c83b90a4d Marc Bilbao Asensio Marc Bilbao Asensio true false 9cfd17551c0d1f7438895121e4fbb6e8 0000-0002-0590-9462 James Cronin James Cronin true false 7fcde209a4da147b056cefdb554f81b5 Saul Michue-Seijas Saul Michue-Seijas true false 14faad807724ffe1fb168c3fc225be0e 0000-0002-7405-3338 Juan Mareque-Rivas Juan Mareque-Rivas true false 2022-10-27 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. Journal Article Advanced Therapeutics 6 2 2200179 Wiley 2366-3987 2366-3987 Ferroptosis; Platinum(IV) prodrugs; Iron oxide nanoparticles; ROS, Lymphatic system; Drug delivery; Melanoma treatment 14 11 2022 2022-11-14 10.1002/adtp.202200179 COLLEGE NANME COLLEGE CODE Swansea University SU Library paid the OA fee (TA Institutional Deal) 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)) 2024-07-15T12:05:12.4026920 2022-10-27T10:52:22.0824373 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Marc Bilbao Asensio 1 Ane Ruiz‐de‐Angulo 2 Amaia Garaikoetxea Arguinzoniz 3 James Cronin 0000-0002-0590-9462 4 Jordi Llop 5 Aintzane Zabaleta 6 Saul Michue-Seijas 7 Dominika Sosnowska 8 James N. Arnold 9 Juan Mareque-Rivas 0000-0002-7405-3338 10 61668__25797__fce6f6f39aa24ea1b52b26fe2e122f60.pdf 61668.pdf 2022-11-16T12:21:38.9843386 Output 4781909 application/pdf Version of Record true © 2022 The Authors. This is an open access article under the terms of the Creative Commons Attribution License true eng http://creativecommons.org/licenses/by/4.0/
title Redox‐Triggered Nanomedicine via Lymphatic Delivery: Inhibition of Melanoma Growth by Ferroptosis Enhancement and a Pt(IV)‐Prodrug Chemoimmunotherapy Approach
spellingShingle Redox‐Triggered Nanomedicine via Lymphatic Delivery: Inhibition of Melanoma Growth by Ferroptosis Enhancement and a Pt(IV)‐Prodrug Chemoimmunotherapy Approach
Marc Bilbao Asensio
James Cronin
Saul Michue-Seijas
Juan Mareque-Rivas
title_short Redox‐Triggered Nanomedicine via Lymphatic Delivery: Inhibition of Melanoma Growth by Ferroptosis Enhancement and a Pt(IV)‐Prodrug Chemoimmunotherapy Approach
title_full Redox‐Triggered Nanomedicine via Lymphatic Delivery: Inhibition of Melanoma Growth by Ferroptosis Enhancement and a Pt(IV)‐Prodrug Chemoimmunotherapy Approach
title_fullStr Redox‐Triggered Nanomedicine via Lymphatic Delivery: Inhibition of Melanoma Growth by Ferroptosis Enhancement and a Pt(IV)‐Prodrug Chemoimmunotherapy Approach
title_full_unstemmed Redox‐Triggered Nanomedicine via Lymphatic Delivery: Inhibition of Melanoma Growth by Ferroptosis Enhancement and a Pt(IV)‐Prodrug Chemoimmunotherapy Approach
title_sort Redox‐Triggered Nanomedicine via Lymphatic Delivery: Inhibition of Melanoma Growth by Ferroptosis Enhancement and a Pt(IV)‐Prodrug Chemoimmunotherapy Approach
author_id_str_mv ae3834a12e3216058248bf0c83b90a4d
9cfd17551c0d1f7438895121e4fbb6e8
7fcde209a4da147b056cefdb554f81b5
14faad807724ffe1fb168c3fc225be0e
author_id_fullname_str_mv ae3834a12e3216058248bf0c83b90a4d_***_Marc Bilbao Asensio
9cfd17551c0d1f7438895121e4fbb6e8_***_James Cronin
7fcde209a4da147b056cefdb554f81b5_***_Saul Michue-Seijas
14faad807724ffe1fb168c3fc225be0e_***_Juan Mareque-Rivas
author Marc Bilbao Asensio
James Cronin
Saul Michue-Seijas
Juan Mareque-Rivas
author2 Marc Bilbao Asensio
Ane Ruiz‐de‐Angulo
Amaia Garaikoetxea Arguinzoniz
James Cronin
Jordi Llop
Aintzane Zabaleta
Saul Michue-Seijas
Dominika Sosnowska
James N. Arnold
Juan Mareque-Rivas
format Journal article
container_title Advanced Therapeutics
container_volume 6
container_issue 2
container_start_page 2200179
publishDate 2022
institution Swansea University
issn 2366-3987
2366-3987
doi_str_mv 10.1002/adtp.202200179
publisher Wiley
college_str Faculty of Science and Engineering
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hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
document_store_str 1
active_str 0
description 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.
published_date 2022-11-14T12:05:11Z
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