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2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy
- Source :
- Bioactive Materials; 20210101, Issue: Preprints
- Publication Year :
- 2021
-
Abstract
- 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®) and the topoisomerase 2 inhibitor, doxorubicin (DOX). Loading DOXjadeonto ultrathin 2D Ti3C2MXene nanosheets produces a construct, Ti3C2-PVP@DOXjade, that allows the iron chelation and chemotherapeutic functions of DOXjadeto 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@DOXjadeserves to promote apoptotic cell death and downregulate the iron depletion-induced iron transferrin receptor (TfR). A tumor pH-responsive iron chelation/PTT/chemotherapy antitumor effect was achieved both in vitroand in vivo. The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.
Details
- Language :
- English
- ISSN :
- 2452199X
- Issue :
- Preprints
- Database :
- Supplemental Index
- Journal :
- Bioactive Materials
- Publication Type :
- Periodical
- Accession number :
- ejs58488079
- Full Text :
- https://doi.org/10.1016/j.bioactmat.2021.12.011