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    靶向PDPN的蛋黄脂质纳米共递药系统构建及其体外抗食管鳞癌效应研究

    Construction of a egg yolk lipid-based co-delivery nano-drug system targeting PDPN and its in vitro anti-esophageal squamous cell carcinoma effects

    • 摘要: 目的 制备共负载平足蛋白(PDPN)小干扰RNA (si-PDPN)及紫杉醇(PTX)的蛋黄脂质纳米共递药系统,探讨其对食管鳞癌(ESCC)传统化疗药物疗效的影响及作用机制。方法 通过TCGA数据库分析PDPN在ESCC组织及癌旁组织中的表达差异并在组织样本中验证;利用小干扰RNA沉默ESCC细胞中PDPN的表达,检测ESCC细胞增殖、迁移及侵袭能力的变化。通过蛋黄脂质纳米载体(EYLNs)共负载紫杉醇及si-PDPN,制备共递药系统EYLNs-PTX-siPDPN。使用粒度仪检测共递药系统的粒径及Zeta电位,并监测14 d内的粒径变化;通过Western blot实验检测EYLNs-PTX-siPDPN的PDPN干扰效率;比较共递药系统对食管鳞癌KYSE150细胞增殖、凋亡、侵袭及迁移能力的影响,评估其抗ESCC效应。结果 ESCC组织及细胞中PDPN的表达显著高于癌旁组织及正常食管上皮细胞;敲低PDPN后,KYSE150细胞的增殖、迁移及侵袭能力显著降低。EYLNs-PTX-siPDPN粒径为(84.5±1.4) nm,电位为(-13.3±1.0) mV,4℃保存下其粒径14 d内无明显变化;此外,可有效递送si-PDPN至肿瘤细胞内并干扰PDPN表达。EYLNs-PTX-siPDPN较PTX及EYLNs-PTX促进ESCC细胞凋亡,对ESCC细胞增殖、侵袭、迁移能力的抑制作用更强。结论 同时携带化疗药物紫杉醇及si-PDPN的共递药系统EYLNs-PTX-siPDPN具有更强的抗ESCC效应。

       

      Abstract: Objective To develop a yolk lipid-based nano co-delivery system co-loaded with podoplanin (PDPN) small interfering RNA (si-PDPN) and paclitaxel (PTX), and to explore its impact on the efficacy and mechanism of traditional chemotherapy against esophageal squamous cell carcinoma (ESCC).Methods The differential expression of PDPN between ESCC tissues and adjacent normal tissues was analyzed using the TCGA database and then validated in tissue samples. ESCC cells with silenced expression of PDPN by siRNA were used to detect changes in cell proliferation, migration, and invasion. A co-delivery drug system (EYLNs-PTX-siPDPN) was constructed by encapsulating PTX and si-PDPN into egg yolk lipid-based nanoparticles (EYLNs). The particle size and zeta potential of the system were measured using a particle size analyzer, and particle stability was monitored over 14 days. The interference efficiency of PDPN by EYLNs-PTX-siPDPN was assessed by Western blot. The effects of the co-delivery system on KYSE150 cell proliferation, apoptosis, invasion, and migration were evaluated to assess its anti-ESCC efficacy.Results PDPN expression was significantly higher in ESCC tissues and cells than in adjacent normal tissues and normal esophageal epithelial cells. Knockdown of PDPN significantly inhibited the proliferation, migration, and invasion of KYSE150 cells. The particle size and zeta potential of EYLNs-PTX-siPDPN were (84.5±1.4) nm and (-13.3±1.0) mV, respectively, and particle size remained stable at 4 ℃ for 14 days. The system effectively delivered si-PDPN into tumor cells and suppressed PDPN expression. Compared with PTX and EYLNs-PTX, EYLNs-PTX-siPDPN significantly enhanced ESCC cell apoptosis and effectively inhibited proliferation, invasion, and migration.Conclusions Conclusions The co-delivery system EYLNs-PTX-siPDPN, which simultaneously delivers paclitaxel and si-PDPN, exhibits enhanced anti-ESCC effects.

       

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