2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35310350.
- Also identified by DOI 10.1016/j.bioactmat.2021.12.011 and PMC identifier 8892152.
- Licence recorded as CC BY-NC-ND.
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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, <b>DOXjade</b>, 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 <b>DOXjade</b> onto ultrathin 2D Ti<sub>3</sub>C<sub>2</sub> MXene nanosheets produces a construct, <b>Ti</b> <sub><b>3</b></sub> <b>C</b> <sub><b>2</b></sub> <b>-PVP@DOXjade</b>, that allows the iron chelation and chemotherapeutic functions of <b>DOXjade</b> 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, <b>Ti</b> <sub><b>3</b></sub> <b>C</b> <sub><b>2</b></sub> <b>-PVP@DOXjade</b> 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 <i>in vitro</i> and <i>in vivo</i>. The results of this study highlight what may constitute a promising iron chelation-based phototherapeutic approach to cancer therapy.