Jahn-Teller distortion-engineered self-propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapy
Mitochondrial metabolism plays a pivotal role in tumor progression, yet effective therapeutic targeting remains constrained by limited tissue penetration and lack of spatiotemporal control. Herein, we present Jahn-Teller distortion-engineered, self-propelled nanorobots (IDP@Z@AP) that integrate cata...
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KeAi Communications Co., Ltd.
2025-12-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25003755 |
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| author | Tianying Luo Mingyi Zhang Jia Xu Dechao Yuan Beibei Yin Yuzhou Zhu Shuang Yan Meng Pan Dong Mo Xicheng Li Xuyue Liang Zhaojuan Qin Hongxin Deng Zhiyong Qian |
| author_facet | Tianying Luo Mingyi Zhang Jia Xu Dechao Yuan Beibei Yin Yuzhou Zhu Shuang Yan Meng Pan Dong Mo Xicheng Li Xuyue Liang Zhaojuan Qin Hongxin Deng Zhiyong Qian |
| author_sort | Tianying Luo |
| collection | DOAJ |
| description | Mitochondrial metabolism plays a pivotal role in tumor progression, yet effective therapeutic targeting remains constrained by limited tissue penetration and lack of spatiotemporal control. Herein, we present Jahn-Teller distortion-engineered, self-propelled nanorobots (IDP@Z@AP) that integrate catalytic oxygen generation, mitochondria-targeted drug delivery, and real-time 3D NIR-II photoacoustic (PA) imaging for precision tumor therapy. The nanorobots are fabricated by co-encapsulating a NIR-II photothermal agent (IR1048) and a mitochondria-targeting chemotherapeutic (DOX-TPP) within a ZIF-8 framework, followed by in situ anchoring of ultrasmall AuPt bimetallic nanozymes. Pt-induced Jahn-Teller distortion modulates the electronic structure of AuPt, enhancing glucose oxidase- and catalase-like activities. Under NIR-II laser irradiation, photothermal-enhanced cascade catalysis drives autonomous motion and catalyzes intratumoral O2 generation, facilitating deep tumor infiltration. In vitro studies reveal efficient mitochondrial targeting, resulting in significant mitochondrial membrane depolarization, intracellular ATP depletion, and suppressed cell migration and invasion. In vivo, 3D NIR-II PA imaging enables noninvasive visualization of nanorobot biodistribution and real-time mapping of catalytic oxygen generation within tumor tissues. This nanorobotic platform effectively modulates tumor hypoxia and enhances chemotherapeutic delivery to mitochondria, ultimately achieving potent tumor suppression. The work offers a smart, catalytically driven, mitochondria-targeted strategy with real-time therapeutic feedback for subcellular-level cancer therapy. |
| format | Article |
| id | doaj-art-29fde982cbd24327a9ebc6fed6811121 |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-29fde982cbd24327a9ebc6fed68111212025-08-23T04:48:46ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-12-015427329010.1016/j.bioactmat.2025.08.021Jahn-Teller distortion-engineered self-propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapyTianying Luo0Mingyi Zhang1Jia Xu2Dechao Yuan3Beibei Yin4Yuzhou Zhu5Shuang Yan6Meng Pan7Dong Mo8Xicheng Li9Xuyue Liang10Zhaojuan Qin11Hongxin Deng12Zhiyong Qian13Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China; Medical Imaging Key Laboratory of Sichuan Province, North Sichuan Medical College, Nanchong, Sichuan, 637000, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Orthopedics, Zigong First People's Hospital, Zigong, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, ChinaMedical Imaging Key Laboratory of Sichuan Province, North Sichuan Medical College, Nanchong, Sichuan, 637000, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China; Corresponding author.Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China; Corresponding author.Mitochondrial metabolism plays a pivotal role in tumor progression, yet effective therapeutic targeting remains constrained by limited tissue penetration and lack of spatiotemporal control. Herein, we present Jahn-Teller distortion-engineered, self-propelled nanorobots (IDP@Z@AP) that integrate catalytic oxygen generation, mitochondria-targeted drug delivery, and real-time 3D NIR-II photoacoustic (PA) imaging for precision tumor therapy. The nanorobots are fabricated by co-encapsulating a NIR-II photothermal agent (IR1048) and a mitochondria-targeting chemotherapeutic (DOX-TPP) within a ZIF-8 framework, followed by in situ anchoring of ultrasmall AuPt bimetallic nanozymes. Pt-induced Jahn-Teller distortion modulates the electronic structure of AuPt, enhancing glucose oxidase- and catalase-like activities. Under NIR-II laser irradiation, photothermal-enhanced cascade catalysis drives autonomous motion and catalyzes intratumoral O2 generation, facilitating deep tumor infiltration. In vitro studies reveal efficient mitochondrial targeting, resulting in significant mitochondrial membrane depolarization, intracellular ATP depletion, and suppressed cell migration and invasion. In vivo, 3D NIR-II PA imaging enables noninvasive visualization of nanorobot biodistribution and real-time mapping of catalytic oxygen generation within tumor tissues. This nanorobotic platform effectively modulates tumor hypoxia and enhances chemotherapeutic delivery to mitochondria, ultimately achieving potent tumor suppression. The work offers a smart, catalytically driven, mitochondria-targeted strategy with real-time therapeutic feedback for subcellular-level cancer therapy.http://www.sciencedirect.com/science/article/pii/S2452199X25003755Self-propelled nanorobotsMitochondria-targetingJahn-Teller distortionBioenergetic disruption3D NIR-II photoacoustic imaging |
| spellingShingle | Tianying Luo Mingyi Zhang Jia Xu Dechao Yuan Beibei Yin Yuzhou Zhu Shuang Yan Meng Pan Dong Mo Xicheng Li Xuyue Liang Zhaojuan Qin Hongxin Deng Zhiyong Qian Jahn-Teller distortion-engineered self-propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapy Bioactive Materials Self-propelled nanorobots Mitochondria-targeting Jahn-Teller distortion Bioenergetic disruption 3D NIR-II photoacoustic imaging |
| title | Jahn-Teller distortion-engineered self-propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapy |
| title_full | Jahn-Teller distortion-engineered self-propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapy |
| title_fullStr | Jahn-Teller distortion-engineered self-propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapy |
| title_full_unstemmed | Jahn-Teller distortion-engineered self-propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapy |
| title_short | Jahn-Teller distortion-engineered self-propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapy |
| title_sort | jahn teller distortion engineered self propelled nanorobots for mitochondrial targeting and bioenergetic disruption in tumor therapy |
| topic | Self-propelled nanorobots Mitochondria-targeting Jahn-Teller distortion Bioenergetic disruption 3D NIR-II photoacoustic imaging |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25003755 |
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