International Journal of Nanomedicine (Sep 2022)

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

  • Gu F,
  • Hu C,
  • Cao W,
  • Li C,
  • Xia Q,
  • Gao Y,
  • Liu Y,
  • Gao S

Journal volume & issue
Vol. Volume 17
pp. 4401 – 4417

Abstract

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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 [email protected]; [email protected]: 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

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