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

• Published in: Bioactive materials 2022-08, Vol.14, p.76-85
• Main Authors: Xu, Yunjie, Wang, Yingwei, An, Jusung, Sedgwick, Adam C., Li, Mingle, Xie, Jianlei, Hu, Weibin, Kang, Jianlong, Sen, Sajal, Steinbrueck, Axel, Zhang, Bin, Qiao, Lijun, Wageh, Swelm, Arambula, Jonathan F., Liu, Liping, Zhang, Han, Sessler, Jonathan L., Kim, Jong Seung
• Format: Article
• Language: English
• Subjects: 2D MXene; Iron chelation; Nanomedicine; Photothermal therapy; Prodrug
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2021.12.011

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. [Display omitted] •A conceptually novel “dual-therapeutic prodrug nanomedicine” strategy was designed for synergistic cancer therapy.•An innovative pH responsive dual-therapeutic conjugate DOXjade was synthesized based on deferasirox and doxorubicin.•Ti3C2-PVP@DOXjade with photoirradiation showed pH-responsive iron chelation/PTT/chemotherapy antitumor effect.•This study thus serves to demonstrate a promising step forward in the development of precise cancer therapies.