Rahdari Tahereh, Mahdavimehr Mohsen, Ghafouri Hossein, Ramezanpour Sorour, Ehtesham Somayeh, Asghari S Mohsen
Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Sci Rep. 2025 Feb 19;15(1):6043. doi: 10.1038/s41598-025-90107-y.
Triple-negative breast cancer (TNBC) presents a global health challenge due to its aggressive behavior and limited treatment options. This study explores a novel therapeutic strategy using C-peptide-conjugated solid lipid nanoparticles (C-peptide-SLNs) for targeting paclitaxel (PTX) delivery in TNBC treatment. C-peptide, derived from endostatin, enhances efficacy by targeting overexpressed integrin αvβ3 receptors on TNBC cells. Characterization confirmed suitable particle size, stability, and encapsulation efficiency over 90%, with favorable release profiles for acidic tumor environments. In vitro, C-peptide-SLN-PTX markedly improved cytotoxicity against 4T1 carcinoma cells, with an IC of 1.2 µg/mL, compared to 3.4 µg/mL for SLN-PTX and 8.9 µg/mL for free PTX. Wound-healing assays verified significant inhibition of cell migration in 4T1 and MDA-MB-231 cell lines. Flow cytometry confirmed αv integrin targeting by C-peptide-SLN-PTX. In vivo studies in 4T1 tumor-bearing mice showed an 82% tumor volume reduction and prevented pulmonary metastasis, with normal liver enzyme levels indicating reduced toxicity. PET imaging revealed decreased tumor metabolic activity in treated groups, and immunohistochemical analyses demonstrated superior antitumor efficacy with reduced Ki-67 expression and apoptosis induction (p53 upregulation, Bcl-2 downregulation). These findings highlight the potential of C-peptide-SLNs as an effective targeted PTX delivery system for TNBC, offering promising avenues for enhancing cancer treatment strategies.
三阴性乳腺癌（TNBC）因其侵袭性和有限的治疗选择而成为一项全球健康挑战。本研究探索了一种新的治疗策略，即使用C肽偶联固体脂质纳米粒（C肽-SLNs）在TNBC治疗中靶向递送紫杉醇（PTX）。源自内皮抑素的C肽通过靶向TNBC细胞上过度表达的整合素αvβ3受体来提高疗效。表征结果证实颗粒大小合适、稳定性良好且包封效率超过90%，在酸性肿瘤环境中具有良好的释放特性。在体外，与SLN-PTX的3.4 μg/mL和游离PTX的8.9 μg/mL相比，C肽-SLN-PTX显著提高了对4T1癌细胞的细胞毒性，IC50为1.2 μg/mL。伤口愈合试验证实对4T1和MDA-MB-231细胞系中的细胞迁移有显著抑制作用。流式细胞术证实C肽-SLN-PTX可靶向αv整合素。在携带4T1肿瘤的小鼠体内进行的研究表明，肿瘤体积减少了82%，并预防了肺转移，正常的肝酶水平表明毒性降低。PET成像显示治疗组肿瘤代谢活性降低，免疫组织化学分析表明具有卓越的抗肿瘤疗效，Ki-67表达降低且诱导了细胞凋亡（p53上调，Bcl-2下调）。这些发现突出了C肽-SLNs作为TNBC有效靶向PTX递送系统的潜力，为增强癌症治疗策略提供了有前景的途径。
