2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy

Yunjie Xu, Yingwei Wang, Jusung An, Adam C. Sedgwick, Mingle Li, Jianlei Xie, Weibin Hu, Jianlong Kang, Sajal Sen, Axel Steinbrueck, Bin Zhang, Lijun Qiao, Swelm Wageh, Jonathan F. Arambula, Liping Liu, Han Zhang, Jonathan L. Sessler, Jong Seung Kim

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)76-85
Number of pages10
JournalBioactive Materials
Volume14
DOIs
Publication statusPublished - 2022 Aug

Keywords

  • 2D MXene
  • Iron chelation
  • Nanomedicine
  • Photothermal therapy
  • Prodrug

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biomedical Engineering

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