Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formation
Abstract Despite many nano-based strategies devoted to delivering cisplatin for tumor therapy, its clinical benefits are compromised by poor tissue penetration and limited DNA adducts formation of the drug. Herein, a cisplatin loading nanomotor based janus structured Ag-polymer is developed for cisp...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01622-3 |
| _version_ | 1811200845115555840 |
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| author | Lihua Xu Kaixiang Zhang Xing Ma Yingying Li Yajie Jin Chenglin Liang Yong Wang Wendi Duan Hongling Zhang Zhenzhong Zhang Jinjin Shi Junjie Liu Yunlong Wang Wentao Li |
| author_facet | Lihua Xu Kaixiang Zhang Xing Ma Yingying Li Yajie Jin Chenglin Liang Yong Wang Wendi Duan Hongling Zhang Zhenzhong Zhang Jinjin Shi Junjie Liu Yunlong Wang Wentao Li |
| author_sort | Lihua Xu |
| collection | DOAJ |
| description | Abstract Despite many nano-based strategies devoted to delivering cisplatin for tumor therapy, its clinical benefits are compromised by poor tissue penetration and limited DNA adducts formation of the drug. Herein, a cisplatin loading nanomotor based janus structured Ag-polymer is developed for cisplatin delivery of deeper tissue and increased DNA adducts formation. The nanomotor displayed a self‐propelled tumor penetration fueled by hydrogen peroxide (H2O2) in tumor tissues, which is catalytically decomposed into a large amount of oxygen bubbles by Ag nanoparticles (NPs). Notably, cisplatin could elevate the intracellular H2O2 level through cascade reactions, further promote the degradation of Ag NPs accompanied with the Ag+ release, which could downregulate intracellular Cl− through the formation of AgCl precipitate, thereby enhancing cisplatin dechlorination and Pt–DNA formation. Moreover, polymer can also inhibit the activity of ALKBH2 (a Fe2+-dependent DNA repair enzyme) by chelating intracellular Fe2+ to increase the proportion of irreparable Pt–DNA cross-links. It is found that deep tissue penetration, as well as the increased formation and maintenance of Pt–DNA adducts induced by the nanomotor afford 80% of tumor growth inhibition with negligible toxicity. This work provides an important perspective of resolving chemotherapeutic barriers for boosting cisplatin therapy. Graphical Abstract |
| first_indexed | 2024-04-12T02:10:36Z |
| format | Article |
| id | doaj.art-ce3c1a95094943a4bb22a25858dd19f0 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-12T02:10:36Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-ce3c1a95094943a4bb22a25858dd19f02022-12-22T03:52:24ZengBMCJournal of Nanobiotechnology1477-31552022-09-0120111710.1186/s12951-022-01622-3Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formationLihua Xu0Kaixiang Zhang1Xing Ma2Yingying Li3Yajie Jin4Chenglin Liang5Yong Wang6Wendi Duan7Hongling Zhang8Zhenzhong Zhang9Jinjin Shi10Junjie Liu11Yunlong Wang12Wentao Li13National Center for International Research in Cell and Gene Therapy, Sino-British Research Center for Molecular Oncology, Academy of Medical Sciences, Zhengzhou UniversitySchool of Pharmaceutical Sciences, Zhengzhou UniversitySchool of Materials Science and Engineering & Flexible Printed Electronic Technology Center, Harbin Institute of Technology (Shenzhen)School of Pharmaceutical Sciences, Zhengzhou UniversitySchool of Pharmaceutical Sciences, Zhengzhou UniversitySchool of Pharmaceutical Sciences, Zhengzhou UniversitySchool of Materials Science and Engineering & Flexible Printed Electronic Technology Center, Harbin Institute of Technology (Shenzhen)School of Materials Science and Engineering & Flexible Printed Electronic Technology Center, Harbin Institute of Technology (Shenzhen)School of Pharmaceutical Sciences, Zhengzhou UniversitySchool of Pharmaceutical Sciences, Zhengzhou UniversitySchool of Pharmaceutical Sciences, Zhengzhou UniversitySchool of Pharmaceutical Sciences, Zhengzhou UniversityHenan Bioengineering Research CenterDepartment of Breast Surgery, Henan Provincial People’s HospitalAbstract Despite many nano-based strategies devoted to delivering cisplatin for tumor therapy, its clinical benefits are compromised by poor tissue penetration and limited DNA adducts formation of the drug. Herein, a cisplatin loading nanomotor based janus structured Ag-polymer is developed for cisplatin delivery of deeper tissue and increased DNA adducts formation. The nanomotor displayed a self‐propelled tumor penetration fueled by hydrogen peroxide (H2O2) in tumor tissues, which is catalytically decomposed into a large amount of oxygen bubbles by Ag nanoparticles (NPs). Notably, cisplatin could elevate the intracellular H2O2 level through cascade reactions, further promote the degradation of Ag NPs accompanied with the Ag+ release, which could downregulate intracellular Cl− through the formation of AgCl precipitate, thereby enhancing cisplatin dechlorination and Pt–DNA formation. Moreover, polymer can also inhibit the activity of ALKBH2 (a Fe2+-dependent DNA repair enzyme) by chelating intracellular Fe2+ to increase the proportion of irreparable Pt–DNA cross-links. It is found that deep tissue penetration, as well as the increased formation and maintenance of Pt–DNA adducts induced by the nanomotor afford 80% of tumor growth inhibition with negligible toxicity. This work provides an important perspective of resolving chemotherapeutic barriers for boosting cisplatin therapy. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01622-3Cisplatin chemotherapyNanomotorTumor penetrationDNA adductIon regulation |
| spellingShingle | Lihua Xu Kaixiang Zhang Xing Ma Yingying Li Yajie Jin Chenglin Liang Yong Wang Wendi Duan Hongling Zhang Zhenzhong Zhang Jinjin Shi Junjie Liu Yunlong Wang Wentao Li Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formation Journal of Nanobiotechnology Cisplatin chemotherapy Nanomotor Tumor penetration DNA adduct Ion regulation |
| title | Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formation |
| title_full | Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formation |
| title_fullStr | Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formation |
| title_full_unstemmed | Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formation |
| title_short | Boosting cisplatin chemotherapy by nanomotor-enhanced tumor penetration and DNA adducts formation |
| title_sort | boosting cisplatin chemotherapy by nanomotor enhanced tumor penetration and dna adducts formation |
| topic | Cisplatin chemotherapy Nanomotor Tumor penetration DNA adduct Ion regulation |
| url | https://doi.org/10.1186/s12951-022-01622-3 |
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