PEG-conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating DOX-induced splenocardiac toxicity in the breast cancer
Doxorubicin (DOX) is an effective chemotherapeutic agent widely used for cancer treatment. However, hypoxia in tumour tissue and obvious adverse effects particularly cardiotoxicity restricts the clinical usage of DOX. Our study is based on the co-administration of haemoglobin-based oxygen carriers (...
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Taylor & Francis Group
2023-12-01
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| Series: | Artificial Cells, Nanomedicine, and Biotechnology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21691401.2023.2176865 |
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| author | Bingting Li Jun Zhang Ning Ma Weidan Li Guoxing You Gan Chen Lian Zhao Quan Wang Hong Zhou |
| author_facet | Bingting Li Jun Zhang Ning Ma Weidan Li Guoxing You Gan Chen Lian Zhao Quan Wang Hong Zhou |
| author_sort | Bingting Li |
| collection | DOAJ |
| description | Doxorubicin (DOX) is an effective chemotherapeutic agent widely used for cancer treatment. However, hypoxia in tumour tissue and obvious adverse effects particularly cardiotoxicity restricts the clinical usage of DOX. Our study is based on the co-administration of haemoglobin-based oxygen carriers (HBOCs) and DOX in a breast cancer model to investigate HBOCs’ ability to enhance chemotherapeutic effectiveness and its capabilities to alleviate the side effects induced by DOX. In an in-vitro study, the results suggested the cytotoxicity of DOX was significantly improved when combined with HBOCs in a hypoxic environment, and produced more γ-H2AX indicating higher DNA damage than free DOX did. Compared with administration of free DOX, combined therapy exhibited a stronger tumour suppressive effect in an in-vivo study. Further mechanism studies showed that the expression of various proteins such as hypoxia-inducible factor-1α (HIF-1α), CD31, CD34, and vascular endothelial growth factor (VEGF) in tumour tissues was also significantly reduced in the combined treatment group. In addition, HBOCs can significantly reduce the splenocardiac toxicity induced by DOX, according to the results of the haematoxylin and eosin (H&E) staining and histological investigation. This study suggested that PEG-conjugated bovine haemoglobin may not only reduce the hypoxia in tumours and increase the efficiency of chemotherapeutic agent DOX, but also alleviate the irreversible heart toxicity caused by DOX-inducted splenocardiac dysregulation. |
| format | Article |
| id | doaj-art-c6cffe8d3b3940c889765348a38f8f5e |
| institution | DOAJ |
| issn | 2169-1401 2169-141X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
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| series | Artificial Cells, Nanomedicine, and Biotechnology |
| spelling | doaj-art-c6cffe8d3b3940c889765348a38f8f5e2025-08-20T03:05:26ZengTaylor & Francis GroupArtificial Cells, Nanomedicine, and Biotechnology2169-14012169-141X2023-12-0151112013010.1080/21691401.2023.2176865PEG-conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating DOX-induced splenocardiac toxicity in the breast cancerBingting Li0Jun Zhang1Ning Ma2Weidan Li3Guoxing You4Gan Chen5Lian Zhao6Quan Wang7Hong Zhou8Institute of Health Service and Transfusion Medicine, Beijing, P. R. ChinaInstitute of Health Service and Transfusion Medicine, Beijing, P. R. ChinaClinical Laboratory of Beijing Huairou Hospital, Beijing, P. R. ChinaInstitute of Health Service and Transfusion Medicine, Beijing, P. R. ChinaInstitute of Health Service and Transfusion Medicine, Beijing, P. R. ChinaInstitute of Health Service and Transfusion Medicine, Beijing, P. R. ChinaInstitute of Health Service and Transfusion Medicine, Beijing, P. R. ChinaInstitute of Health Service and Transfusion Medicine, Beijing, P. R. ChinaInstitute of Health Service and Transfusion Medicine, Beijing, P. R. ChinaDoxorubicin (DOX) is an effective chemotherapeutic agent widely used for cancer treatment. However, hypoxia in tumour tissue and obvious adverse effects particularly cardiotoxicity restricts the clinical usage of DOX. Our study is based on the co-administration of haemoglobin-based oxygen carriers (HBOCs) and DOX in a breast cancer model to investigate HBOCs’ ability to enhance chemotherapeutic effectiveness and its capabilities to alleviate the side effects induced by DOX. In an in-vitro study, the results suggested the cytotoxicity of DOX was significantly improved when combined with HBOCs in a hypoxic environment, and produced more γ-H2AX indicating higher DNA damage than free DOX did. Compared with administration of free DOX, combined therapy exhibited a stronger tumour suppressive effect in an in-vivo study. Further mechanism studies showed that the expression of various proteins such as hypoxia-inducible factor-1α (HIF-1α), CD31, CD34, and vascular endothelial growth factor (VEGF) in tumour tissues was also significantly reduced in the combined treatment group. In addition, HBOCs can significantly reduce the splenocardiac toxicity induced by DOX, according to the results of the haematoxylin and eosin (H&E) staining and histological investigation. This study suggested that PEG-conjugated bovine haemoglobin may not only reduce the hypoxia in tumours and increase the efficiency of chemotherapeutic agent DOX, but also alleviate the irreversible heart toxicity caused by DOX-inducted splenocardiac dysregulation.https://www.tandfonline.com/doi/10.1080/21691401.2023.2176865Doxorubicintumour hypoxiaHBOCscardiotoxicitysplenic toxicity |
| spellingShingle | Bingting Li Jun Zhang Ning Ma Weidan Li Guoxing You Gan Chen Lian Zhao Quan Wang Hong Zhou PEG-conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating DOX-induced splenocardiac toxicity in the breast cancer Artificial Cells, Nanomedicine, and Biotechnology Doxorubicin tumour hypoxia HBOCs cardiotoxicity splenic toxicity |
| title | PEG-conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating DOX-induced splenocardiac toxicity in the breast cancer |
| title_full | PEG-conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating DOX-induced splenocardiac toxicity in the breast cancer |
| title_fullStr | PEG-conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating DOX-induced splenocardiac toxicity in the breast cancer |
| title_full_unstemmed | PEG-conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating DOX-induced splenocardiac toxicity in the breast cancer |
| title_short | PEG-conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating DOX-induced splenocardiac toxicity in the breast cancer |
| title_sort | peg conjugated bovine haemoglobin enhances efficiency of chemotherapeutic agent doxorubicin with alleviating dox induced splenocardiac toxicity in the breast cancer |
| topic | Doxorubicin tumour hypoxia HBOCs cardiotoxicity splenic toxicity |
| url | https://www.tandfonline.com/doi/10.1080/21691401.2023.2176865 |
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