Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast Cancer
Fenfen Gu,1,* Chuling Hu,2,* Wei Cao,3,* Chao Li,1 Qingming Xia,4 Yuan Gao,4 Yan Liu,1 Shen Gao1,4 1Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Jiaxing Maternity and Chi...
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Dove Medical Press
2022-09-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/tumor-microenvironment-multiple-responsive-nanoparticles-for-targeted--peer-reviewed-fulltext-article-IJN |
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| author | Gu F Hu C Cao W Li C Xia Q Gao Y Liu Y Gao S |
| author_facet | Gu F Hu C Cao W Li C Xia Q Gao Y Liu Y Gao S |
| author_sort | Gu F |
| collection | DOAJ |
| description | Fenfen Gu,1,* Chuling Hu,2,* Wei Cao,3,* Chao Li,1 Qingming Xia,4 Yuan Gao,4 Yan Liu,1 Shen Gao1,4 1Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Jiaxing Maternity and Child Health Care Hospital, Jiaxing, People’s Republic of China; 3Department of Neurovascular Disease, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shen Gao; Yan Liu, Tel/Fax +86 21 81873715 ; +86 21 25077156, Email liullk@126.com; liuyan03@xinhuamed.com.cnIntroduction: Currently, the main treatment for advanced breast cancer is still chemotherapy. Immunological and chemical combination therapy has a coordinated therapeutic effect and achieves some efficacy. However, the immunosuppressive tumor microenvironment is a major cause for the failure of immunotherapy in breast cancer. CpG oligodeoxynucleotides can activate the tumor immune microenvironment to reverse the failure of immunotherapy.Methods: In this study, we designed an amphiphilic peptide micelle system (Co-LMs), which can targeted delivery of the immune adjuvant CpG and the chemotherapeutic drug doxorubicin to breast cancer tumors simultaneously. The peptide micelle system achieved tumor microenvironment pH and redox-sensitive drug release.Results and Discussion: Co-LMs showed 2.3 times the antitumor efficacy of chemotherapy alone and 5.1 times the antitumor efficacy of immunotherapy alone in triple-negative breast cancer mice. Co-LMs activated cytotoxic CD8+ T lymphocytes and CD4+ T cells in mice to a greater extent than single treatments. We also found that Co-LMs inhibited the metastasis of circulating tumor cells in the bloodstream to some extent. These results indicate that the Co-LMs offer a promising therapeutic strategy against triple-negative breast cancer.Keywords: chemo-immunotherapy, tumor microenvironment, CpG, nanoparticles, triple-negative breast cancer |
| first_indexed | 2024-04-11T09:22:44Z |
| format | Article |
| id | doaj.art-8b6e94e88ea84c448b01c4ac4925a965 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-04-11T09:22:44Z |
| publishDate | 2022-09-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-8b6e94e88ea84c448b01c4ac4925a9652022-12-22T04:32:08ZengDove Medical PressInternational Journal of Nanomedicine1178-20132022-09-01Volume 174401441778393Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast CancerGu FHu CCao WLi CXia QGao YLiu YGao SFenfen Gu,1,* Chuling Hu,2,* Wei Cao,3,* Chao Li,1 Qingming Xia,4 Yuan Gao,4 Yan Liu,1 Shen Gao1,4 1Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Jiaxing Maternity and Child Health Care Hospital, Jiaxing, People’s Republic of China; 3Department of Neurovascular Disease, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shen Gao; Yan Liu, Tel/Fax +86 21 81873715 ; +86 21 25077156, Email liullk@126.com; liuyan03@xinhuamed.com.cnIntroduction: Currently, the main treatment for advanced breast cancer is still chemotherapy. Immunological and chemical combination therapy has a coordinated therapeutic effect and achieves some efficacy. However, the immunosuppressive tumor microenvironment is a major cause for the failure of immunotherapy in breast cancer. CpG oligodeoxynucleotides can activate the tumor immune microenvironment to reverse the failure of immunotherapy.Methods: In this study, we designed an amphiphilic peptide micelle system (Co-LMs), which can targeted delivery of the immune adjuvant CpG and the chemotherapeutic drug doxorubicin to breast cancer tumors simultaneously. The peptide micelle system achieved tumor microenvironment pH and redox-sensitive drug release.Results and Discussion: Co-LMs showed 2.3 times the antitumor efficacy of chemotherapy alone and 5.1 times the antitumor efficacy of immunotherapy alone in triple-negative breast cancer mice. Co-LMs activated cytotoxic CD8+ T lymphocytes and CD4+ T cells in mice to a greater extent than single treatments. We also found that Co-LMs inhibited the metastasis of circulating tumor cells in the bloodstream to some extent. These results indicate that the Co-LMs offer a promising therapeutic strategy against triple-negative breast cancer.Keywords: chemo-immunotherapy, tumor microenvironment, CpG, nanoparticles, triple-negative breast cancerhttps://www.dovepress.com/tumor-microenvironment-multiple-responsive-nanoparticles-for-targeted--peer-reviewed-fulltext-article-IJNchemo-immunotherapytumor microenvironmentcpgnanoparticlestriple-negative breast cancer |
| spellingShingle | Gu F Hu C Cao W Li C Xia Q Gao Y Liu Y Gao S Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast Cancer International Journal of Nanomedicine chemo-immunotherapy tumor microenvironment cpg nanoparticles triple-negative breast cancer |
| title | Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast Cancer |
| title_full | Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast Cancer |
| title_fullStr | Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast Cancer |
| title_full_unstemmed | Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast Cancer |
| title_short | Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast Cancer |
| title_sort | tumor microenvironment multiple responsive nanoparticles for targeted delivery of doxorubicin and cpg against triple negative breast cancer |
| topic | chemo-immunotherapy tumor microenvironment cpg nanoparticles triple-negative breast cancer |
| url | https://www.dovepress.com/tumor-microenvironment-multiple-responsive-nanoparticles-for-targeted--peer-reviewed-fulltext-article-IJN |
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