2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal 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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2022-08-01
|
| Series: | Bioactive Materials |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X21005831 |
| _version_ | 1827280394886578176 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Yunjie Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T01:11:32Z |
| format | Article |
| id | doaj.art-d782771aa4954029b1ade144caa4c826 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:36:07Z |
| publishDate | 2022-08-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-d782771aa4954029b1ade144caa4c8262024-04-16T17:16:33ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2022-08-011476852D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapyYunjie Xu0Yingwei Wang1Jusung An2Adam C. Sedgwick3Mingle Li4Jianlei Xie5Weibin Hu6Jianlong Kang7Sajal Sen8Axel Steinbrueck9Bin Zhang10Lijun Qiao11Swelm Wageh12Jonathan F. Arambula13Liping Liu14Han Zhang15Jonathan L. Sessler16Jong Seung Kim17Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics; International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education, Shenzhen Institute of Translational Medicine, Department of Otolaryngology, Shenzhen Second People's Hospital, The First Affiliated Hospital, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China; Department of Chemistry, Korea University, Seoul, 02841, South KoreaHunan Key Laboratory of Nanophotonics and Devices, School of Physics and Electronics, Central South University, 932 South Lushan Road, Changsha, 410083, ChinaDepartment of Chemistry, Korea University, Seoul, 02841, South KoreaDepartment of Chemistry, The University of Texas at Austin, Austin, TX, 78712-1224, USADepartment of Chemistry, Korea University, Seoul, 02841, South KoreaShenzhen Engineering Laboratory of Phosphorene and Optoelectronics; International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education, Shenzhen Institute of Translational Medicine, Department of Otolaryngology, Shenzhen Second People's Hospital, The First Affiliated Hospital, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, ChinaShenzhen Engineering Laboratory of Phosphorene and Optoelectronics; International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education, Shenzhen Institute of Translational Medicine, Department of Otolaryngology, Shenzhen Second People's Hospital, The First Affiliated Hospital, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, ChinaDepartment of Chemistry, The University of Texas at Austin, Austin, TX, 78712-1224, USADepartment of Chemistry, The University of Texas at Austin, Austin, TX, 78712-1224, USAInstitute of Translation Medicine Shenzhen Second People's Hospital First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, ChinaDepartment of Physics, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi ArabiaDepartment of Chemistry, The University of Texas at Austin, Austin, TX, 78712-1224, USA; Corresponding author.Department of Hepatobiliary and Pancreatic Surgery, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, 518020, China; Corresponding author.Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics; International Collaborative Laboratory of 2D Materials for Optoelectronics Science and Technology of Ministry of Education, Shenzhen Institute of Translational Medicine, Department of Otolaryngology, Shenzhen Second People's Hospital, The First Affiliated Hospital, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China; Corresponding author.Department of Chemistry, The University of Texas at Austin, Austin, TX, 78712-1224, USA; Corresponding author.Department of Chemistry, Korea University, Seoul, 02841, South Korea; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2452199X210058312D MXeneNanomedicineProdrugIron chelationPhotothermal therapy |
| spellingShingle | 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 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy Bioactive Materials 2D MXene Nanomedicine Prodrug Iron chelation Photothermal therapy |
| title | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
| title_full | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
| title_fullStr | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
| title_full_unstemmed | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
| title_short | 2D-ultrathin MXene/DOXjade platform for iron chelation chemo-photothermal therapy |
| title_sort | 2d ultrathin mxene doxjade platform for iron chelation chemo photothermal therapy |
| topic | 2D MXene Nanomedicine Prodrug Iron chelation Photothermal therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X21005831 |
| work_keys_str_mv | AT yunjiexu 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT yingweiwang 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT jusungan 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT adamcsedgwick 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT mingleli 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT jianleixie 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT weibinhu 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT jianlongkang 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT sajalsen 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT axelsteinbrueck 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT binzhang 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT lijunqiao 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT swelmwageh 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT jonathanfarambula 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT lipingliu 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT hanzhang 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT jonathanlsessler 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy AT jongseungkim 2dultrathinmxenedoxjadeplatformforironchelationchemophotothermaltherapy |