Chemotherapeutic drug scavenger-based combination therapy toward treating triple-negative breast cancer
Abstract Triple-negative breast cancer (TNBC) is resistant to most antitumor treatments, leaving chemotherapy as the primary option. Although doxorubicin (Dox) in combination with other therapies is promising for TNBC management, the combined effect is still compromised by the dose-limiting toxiciti...
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| Language: | English |
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BMC
2025-07-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03571-z |
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| author | Qingqing Yin Yutong Zhong Mengchun Chen Weian Mao Yuan Yang Li Li Dongyan Tian Shuangshuang Liu Ying Chen Jiale Quan Shiyu Li Deli Zhuge Xufei Zhang Ledan Wang Fang Wang Yiming Chen Xiaosheng Lu Xiaoji Lin Yijie Chen Linzhi Yan |
| author_facet | Qingqing Yin Yutong Zhong Mengchun Chen Weian Mao Yuan Yang Li Li Dongyan Tian Shuangshuang Liu Ying Chen Jiale Quan Shiyu Li Deli Zhuge Xufei Zhang Ledan Wang Fang Wang Yiming Chen Xiaosheng Lu Xiaoji Lin Yijie Chen Linzhi Yan |
| author_sort | Qingqing Yin |
| collection | DOAJ |
| description | Abstract Triple-negative breast cancer (TNBC) is resistant to most antitumor treatments, leaving chemotherapy as the primary option. Although doxorubicin (Dox) in combination with other therapies is promising for TNBC management, the combined effect is still compromised by the dose-limiting toxicities of Dox. Here, we developed a chemotherapeutic drug scavenger (CDS) by encapsulating GC-rich DNA—preferred binding targets of Dox—within an erythrocyte membrane functionalized with a normal tissue-targeting (NTT) peptide. Mimicking the structure of the cell nucleus, CDS selectively absorbs and neutralizes Dox in susceptible normal organs while sparing tumor tissues. This targeted detoxification allows for safe escalation of the Dox dose to 15 mg/kg, three times the standard 5 mg/kg, without observable toxicity. Such a high Dox dose enabled by CDS pretreatment significantly inhibited the post-operative residual/metastasized 4T1 tumor growth, regardless of the early or later stages of the tumor. Also, delivery of a high dose of Dox into the 4T1 tumor could profoundly increase the G2/M arrest, facilitating the combination therapy with a low-powered radiation of 2 Gy. Further, tumor exposure to high Dox amounts could convert the 4T1 tumor microenvironment from ‘cold’ to ‘hot’, leading to improved infiltration of immune cells, including T cells, dendritic cells, and macrophages. Overall, this study demonstrates how the safe injection of high amounts of Dox enabled by CDS detoxification could augment and extend Dox’s functionality combined with surgery, radiotherapy, and cell therapy for TNBC treatment. |
| format | Article |
| id | doaj-art-ce819e779b5c4d99bf78bee36763bef6 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-ce819e779b5c4d99bf78bee36763bef62025-08-20T04:01:41ZengBMCJournal of Nanobiotechnology1477-31552025-07-0123111710.1186/s12951-025-03571-zChemotherapeutic drug scavenger-based combination therapy toward treating triple-negative breast cancerQingqing Yin0Yutong Zhong1Mengchun Chen2Weian Mao3Yuan Yang4Li Li5Dongyan Tian6Shuangshuang Liu7Ying Chen8Jiale Quan9Shiyu Li10Deli Zhuge11Xufei Zhang12Ledan Wang13Fang Wang14Yiming Chen15Xiaosheng Lu16Xiaoji Lin17Yijie Chen18Linzhi Yan19Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Chemotherapy and Radiotherapy, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Pharmaceutics, School of Pharmaceutical Sciences of Wenzhou, Medical UniversityWenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityWenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityZhejiang Engineering Research Center for Innovation and Application of Intelligent Radiotherapy Technology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical UniversityAbstract Triple-negative breast cancer (TNBC) is resistant to most antitumor treatments, leaving chemotherapy as the primary option. Although doxorubicin (Dox) in combination with other therapies is promising for TNBC management, the combined effect is still compromised by the dose-limiting toxicities of Dox. Here, we developed a chemotherapeutic drug scavenger (CDS) by encapsulating GC-rich DNA—preferred binding targets of Dox—within an erythrocyte membrane functionalized with a normal tissue-targeting (NTT) peptide. Mimicking the structure of the cell nucleus, CDS selectively absorbs and neutralizes Dox in susceptible normal organs while sparing tumor tissues. This targeted detoxification allows for safe escalation of the Dox dose to 15 mg/kg, three times the standard 5 mg/kg, without observable toxicity. Such a high Dox dose enabled by CDS pretreatment significantly inhibited the post-operative residual/metastasized 4T1 tumor growth, regardless of the early or later stages of the tumor. Also, delivery of a high dose of Dox into the 4T1 tumor could profoundly increase the G2/M arrest, facilitating the combination therapy with a low-powered radiation of 2 Gy. Further, tumor exposure to high Dox amounts could convert the 4T1 tumor microenvironment from ‘cold’ to ‘hot’, leading to improved infiltration of immune cells, including T cells, dendritic cells, and macrophages. Overall, this study demonstrates how the safe injection of high amounts of Dox enabled by CDS detoxification could augment and extend Dox’s functionality combined with surgery, radiotherapy, and cell therapy for TNBC treatment.https://doi.org/10.1186/s12951-025-03571-zTriple-negative breast cancerChemotherapeutic drugDetoxificationBiomimeticCombination therapy |
| spellingShingle | Qingqing Yin Yutong Zhong Mengchun Chen Weian Mao Yuan Yang Li Li Dongyan Tian Shuangshuang Liu Ying Chen Jiale Quan Shiyu Li Deli Zhuge Xufei Zhang Ledan Wang Fang Wang Yiming Chen Xiaosheng Lu Xiaoji Lin Yijie Chen Linzhi Yan Chemotherapeutic drug scavenger-based combination therapy toward treating triple-negative breast cancer Journal of Nanobiotechnology Triple-negative breast cancer Chemotherapeutic drug Detoxification Biomimetic Combination therapy |
| title | Chemotherapeutic drug scavenger-based combination therapy toward treating triple-negative breast cancer |
| title_full | Chemotherapeutic drug scavenger-based combination therapy toward treating triple-negative breast cancer |
| title_fullStr | Chemotherapeutic drug scavenger-based combination therapy toward treating triple-negative breast cancer |
| title_full_unstemmed | Chemotherapeutic drug scavenger-based combination therapy toward treating triple-negative breast cancer |
| title_short | Chemotherapeutic drug scavenger-based combination therapy toward treating triple-negative breast cancer |
| title_sort | chemotherapeutic drug scavenger based combination therapy toward treating triple negative breast cancer |
| topic | Triple-negative breast cancer Chemotherapeutic drug Detoxification Biomimetic Combination therapy |
| url | https://doi.org/10.1186/s12951-025-03571-z |
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