期刊
BIOACTIVE MATERIALS
卷 14, 期 -, 页码 76-85出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.12.011
关键词
2D MXene; Nanomedi cine; Prodrug; Iron chelation; Photothermal therapy
资金
- National Natural Science Foundation of China [11904239]
- Creative Research Initiative of National Research Foundation of Korea (NRF) (CRI project) [2018R1A3B1052702]
- National Institutes of Health [CA 68682]
- Robert A. Welch Foundation [F-0018]
- Brain Pool Program - Ministry of Science and ICT [2020H1D3A1A02080172]
This study reports a dual-therapeutic prodrug that enables iron chelation chemotherapy and photothermal cancer therapy to be photo-activated. It offers a promising iron chelation-based phototherapeutic approach to cancer therapy.
An increased demand for iron is a hallmark of cancer cells and is thought necessary to promote high cell proliferation, tumor progression and metastasis. This makes iron metabolism an attractive therapeutic target. Unfortunately, current iron-based therapeutic strategies often lack effectiveness and can elicit off-target toxicities. We report here a dual-therapeutic prodrug, DOXjade, that allows for iron chelation chemo-photothermal cancer therapy. This prodrug takes advantage of the clinically approved iron chelator deferasirox (ExJade (R)) and the topoisomerase 2 inhibitor, doxorubicin (DOX). Loading DOXjade onto ultrathin 2D Ti3C2 MXene nanosheets produces a construct, Ti3C2-PVP@DOXjade, that allows the iron chelation and chemotherapeutic functions of DOXjade to be photo-activated at the tumor sites, while potentiating a robust photothermal effect with photothermal conversion efficiencies of up to 40%. Antitumor mechanistic investigations reveal that upon activation, Ti3C2-PVP@DOXjade serves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor (TfR). A tumor pH-responsive iron chelation/photothermal/chemotherapy antitumor effect was achieved both in vitro and in vivo. The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.
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