This study aimed to develop, evaluate, and optimize the mPEG-PLA/vitamin E-TPGS mixed micelle drug delivery system to encapsulate celecoxib (CXB) and honokiol (HNK) for intravenous treatment of breast cancer. To this end, we formulated CXB-loaded mPEG-PLA/vitamin E-TPGS (PV-CXB) and HNK-loaded mPEG-PLA/vitamin E-TPGS (PV-HNK) mixed micelles and analyzed their characteristics. The 4T1 cell line was used for cytotoxicity determination and cellular uptake experiments, and for establishing a 4T1-bearing mouse model for histopathology, immunofluorescence, terminal deoxynucleotidyl transferase-mediated nick end labeling, and Western blot analysis. The synergistic effects of PV-CXB and PV-HNK combination therapy were investigated in vitro and in vivo using the coefficient of drug interaction values. The mean size of PV-CXB and PV-HNK prepared with optimal formulation was approximately 50 nm, with a spherical shape. PV-CXB and PV-HNK combination therapy exhibited cytotoxicity in 4T1 cells in vitro. However, the toxicity of PV-CXB and PV-HNK combination therapy was not apparent in normal tissues (heart, liver, spleen, lung, and kidney) in vivo and reduced the expression of collagen fibers in tumor tissues. Moreover, the combination therapy reduced the expression of tumor growth biomarkers (Foxp3, CD4, Gr-1, CD11b, CD31, Ki67, FoxM1, and VEGF). In addition, the tumor cell apoptosis rate reached 45.71 ± 0.62%. The combined treatment with PV-CXB and PV-HNK showed synergistic effect both in vitro and in vivo. Thus, the PV-CXB and PV-HNK drug delivery system could be used as a potential combination therapy for breast cancer .

中文翻译：

---

调整基于mPEG-PLA /维生素E-TPGS的混合胶束用于塞来昔布/厚朴酚联合治疗乳腺癌。

这项研究旨在开发，评估和优化mPEG-PLA /维生素E-TPGS混合胶束药物递送系统，以封装塞来昔布（CXB）和厚朴酚（HNK）用于静脉内治疗乳腺癌。为此，我们配制了CXB负载的mPEG-PLA /维生素E-TPGS（PV-CXB）和HNK负载的mPEG-PLA /维生素E-TPGS（PV-HNK）混合胶束，并分析了它们的特性。4T1细胞系用于细胞毒性测定和细胞摄取实验，并用于建立带有4T1的小鼠模型用于组织病理学，免疫荧光，末端脱氧核苷酸转移酶介导的切口末端标记和Western blot分析。使用药物相互作用值系数在体内和体外研究了PV-CXB和PV-HNK联合治疗的协同作用。用最佳配方制备的PV-CXB和PV-HNK的平均尺寸约为50 nm，呈球形。PV-CXB和PV-HNK联合治疗在体外对4T1细胞表现出细胞毒性。然而，PV-CXB和PV-HNK联合疗法的毒性在体内正常组织（心脏，肝脏，脾脏，肺和肾脏）中不明显，并且降低了肿瘤组织中胶原纤维的表达。此外，联合疗法降低了肿瘤生长生物标志物（Foxp3，CD4，Gr-1，CD11b，CD31，Ki67，FoxM1和VEGF）的表达。另外，肿瘤细胞凋亡率达到45.71±0.62％。PV-CXB和PV-HNK的联合治疗在体外和体内均显示出协同作用。因此，PV-CXB和PV-HNK药物递送系统可以用作乳腺癌的潜在联合疗法。