Immunotherapy is an emerging approach for the treatment of solid tumors. Although chemotherapy is generally considered immunosuppressive, specific chemotherapeutic agents can induce tumor immunity. In this study, we developed a targeted, acid-sensitive peptide nanoparticle (DT/Pep1) to deliver doxorubicin (DOX) and triptolide (TPL) to breast cancer cells the enhanced permeability and retention (EPR) effect and the breast cancer-targeting effect of peptide D8. Compared with administration of the free drugs, treatment with the DT/Pep1 system increased the accumulation of DOX and TPL at the tumor site and achieved deeper penetration into the tumor tissue. In an acidic environment, DT/Pep1 transformed from spherical nanoparticles to aggregates with a high aspect ratio, which successfully extended the retention of the drugs in the tumor cells and bolstered the anticancer effect. In both and experiments, DT/Pep1 effectively blocked the cell cycle and induced apoptosis. Importantly, the DT/Pep1 system efficiently suppressed tumor development in mice bearing 4T1 tumors while simultaneously promoting immune system activation. Thus, the results of this study provide a system for breast cancer therapy and offer a novel and promising platform for peptide nanocarrier-based drug delivery.

中文翻译：

---

靶向载药肽诱导肿瘤细胞凋亡和免疫调节以提高抗肿瘤功效

免疫疗法是治疗实体瘤的新兴方法。尽管化疗通常被认为是免疫抑制性的，但特定的化疗药物可以诱导肿瘤免疫。在这项研究中，我们开发了一种靶向酸敏感肽纳米颗粒（DT/Pep1），将阿霉素（DOX）和雷公藤甲素（TPL）递送至乳腺癌细胞，增强渗透性和保留（EPR）效应以及乳腺癌靶向效应肽D8。与给予游离药物相比，DT/Pep1系统治疗增加了DOX和TPL在肿瘤部位的积累，并实现了对肿瘤组织的更深入的渗透。在酸性环境下，DT/Pep1从球形纳米颗粒转变为高长径比的聚集体，成功延长了药物在肿瘤细胞中的保留时间，增强了抗癌作用。在这两个实验中，DT/Pep1 有效地阻断了细胞周期并诱导细胞凋亡。重要的是，DT/Pep1 系统有效抑制了携带 4T1 肿瘤的小鼠的肿瘤发展，同时促进免疫系统激活。因此，这项研究的结果为乳腺癌治疗提供了一个系统，并为基于肽纳米载体的药物输送提供了一个新颖且有前途的平台。