Tumor Microenvironment Multiple Responsive Nanoparticles for Targeted Delivery of Doxorubicin and CpG Against Triple-Negative Breast Cancer

Introduction: 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 immu...

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Bibliographic Details
Published in:International journal of nanomedicine 2022-01, Vol.17, p.4401-4417
Main Authors: Gu, Fenfen, Hu, Chuling, Cao, Wei, Li, Chao, Xia, Qingming, Gao, Yuan, Liu, Yan, Gao, Shen
Format: Article
Language:English
Subjects:
Antibiotics
Biochemistry
Breast cancer
Cancer
Cancer therapies
chemo-immunotherapy
Chemotherapy
cpg
Drug delivery systems
Drug resistance
Health aspects
Immunotherapy
Laboratory animals
Metastasis
Nanoparticles
Original Research
Peptides
Polyethylene glycol
T cells
Toxicity
triple-negative breast cancer
tumor microenvironment
Tumors
Womens health
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Summary:Introduction: 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.sup.+] T lymphocytes and [CD4.sup.+] 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
ISSN:1178-2013
1176-9114
1178-2013
DOI:10.2147/IJN.S377702