Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Jiaxing Maternity and Child Health Care Hospital, Jiaxing, People's Republic of China.
Int J Nanomedicine. 2022 Sep 20;17:4401-4417. doi: 10.2147/IJN.S377702. eCollection 2022.
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.
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.
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.
目前，晚期乳腺癌的主要治疗方法仍是化疗。免疫与化学联合治疗具有协同治疗作用，并取得了一定疗效。然而，免疫抑制性肿瘤微环境是乳腺癌免疫治疗失败的主要原因。CpG 寡脱氧核苷酸可以激活肿瘤免疫微环境，从而逆转免疫治疗的失败。
在本研究中，我们设计了一种两亲肽胶束系统（Co-LMs），它可以同时靶向递送至乳腺癌肿瘤的免疫佐剂 CpG 和化疗药物阿霉素。该肽胶束系统实现了肿瘤微环境 pH 值和氧化还原敏感的药物释放。
在三阴性乳腺癌小鼠中，Co-LMs 的抗肿瘤疗效是单独化疗的 2.3 倍，是单独免疫治疗的 5.1 倍。Co-LMs 比单一治疗更能激活小鼠中的细胞毒性 CD8+T 淋巴细胞和 CD4+T 细胞。我们还发现，Co-LMs 在一定程度上抑制了循环肿瘤细胞在血液中的转移。这些结果表明，Co-LMs 为治疗三阴性乳腺癌提供了一种很有前途的治疗策略。
