Yang Bowen, Yin Shanmei, Zhou Zishuo, Huang Luyao, Xi Mingrong
Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China.
Cancers (Basel). 2023 Apr 4;15(7):2136. doi: 10.3390/cancers15072136.
The aim is to use E-selectin-binding peptide (ESBP) to actively recognize E-selectin, so allowing a drug delivery system to actively recognize the cells and inhibit the tumor growth of ovarian cancer by targeting adhesion molecules of E-selectin. An ovarian-cancer-directed drug delivery system was designed based on the high affinity of E-selectin-binding peptide (ESBP) to E-selectin. The effects and mechanisms of ESBP-bovine serum albumin (BSA) polymerized nanoparticles were investigated.
BSA polymerized nanoparticles (BSANPs) and ESBP-BSANPs-paclitaxel (PTX) were prepared and their characteristics were measured. The in vitro targetability and cytotoxicity of ESBP-BSANPs-PTX were evaluated through in vitro drug uptake and MTT experiments. The mechanisms of ESBP-BSANPs-PTX were investigated via apoptosis, wound healing and immunohistochemistry assays. The in vivo targeting properties and drug effects were observed in a mouse tumor-bearing model.
In vitro experiments revealed an increase in the uptake of ESBP-BSANPs-FITC. The cytotoxicity of ESBP-BSANPs-PTX in A2780/CP70, HUVEC, RAW264.7 and ID8 cells was higher than that of PTX alone. ESBP-BSANPs-PTX increased cell apoptosis in a dose-dependent manner and exhibited a greater ability to inhibit cell migration than BSANPs-PTX. In vivo experiments demonstrated the targetability and good effects of ESBP-BSANPs.
ESBP-BSANPs-PTX improve PTX targetability, provide tumor-specific and potent therapeutic activities, and show promise for the development of agents in preclinical epithelial ovarian cancer.
利用E选择素结合肽(ESBP)主动识别E选择素,从而使药物递送系统能够通过靶向E选择素的黏附分子来主动识别细胞并抑制卵巢癌的肿瘤生长。基于E选择素结合肽(ESBP)对E选择素的高亲和力,设计了一种靶向卵巢癌的药物递送系统。研究了ESBP-牛血清白蛋白(BSA)聚合纳米粒的作用及机制。
制备BSA聚合纳米粒(BSANPs)和ESBP-BSANPs-紫杉醇(PTX),并测定其特性。通过体外药物摄取和MTT实验评估ESBP-BSANPs-PTX的体外靶向性和细胞毒性。通过凋亡、伤口愈合和免疫组织化学分析研究ESBP-BSANPs-PTX的作用机制。在荷瘤小鼠模型中观察其体内靶向特性和药物效果。
体外实验显示ESBP-BSANPs-FITC的摄取增加。ESBP-BSANPs-PTX对A2780/CP70、人脐静脉内皮细胞(HUVEC)、RAW264.7和ID8细胞的细胞毒性高于单独的PTX。ESBP-BSANPs-PTX以剂量依赖性方式增加细胞凋亡,并且比BSANPs-PTX表现出更强的抑制细胞迁移的能力。体内实验证明了ESBP-BSANPs的靶向性和良好效果。
ESBP-BSANPs-PTX提高了PTX的靶向性,提供了肿瘤特异性和强效治疗活性,并且在临床前上皮性卵巢癌药物开发方面显示出前景。