Department of Otolaryngology, Linyi People's Hospital, Linyi, Shandong, China.
Department of Internal Medicine, Linyi People's Hospital, Linyi, Shandong, China.
Biomed Pharmacother. 2019 Jun;114:108820. doi: 10.1016/j.biopha.2019.108820. Epub 2019 Apr 2.
Current treatment of advanced-stage nasopharyngeal carcinoma (NPC) is not satisfactory. Here, we developed a folic acid (FA) modified, gefitinib (GEF) and yttrium 90 (Y90) co-loaded, core-shell structured lipid-polymer hybrid nanoparticles (FA-GEF-Y90-LPNP). The size and zeta potential, drug release behavior, and uptake by tumor cells were investigated. The antitumor efficiency and toxicity of LPNP were evaluated in cancer cells and in tumor bearing mice. FA-GEF-Y90-LPNP with a mean size of 150 nm and zeta potential of -40 mV was able to enhance the accumulation in the NPC cells and exhibited the highest cytotoxicity. The AUC and T of FA-GEF-Y90-LPNP group was 217.62 ± 10.32 mg/L.h and 12.09 ± 0.43 h, respectively. FA-GEF-Y90-LPNP exhibited the best in vivo tumor inhibition ability, leading to a 221.2 ± 13.5 mm of tumor volume at day 21. FA-GEF-Y90-LPNP treatment resulted in almost no difference in the body weight. This may be the evidence that the systemic toxicity of FA-GEF-Y90-LPNP is low and may be used as safety system for the treatment of NPC.
目前,晚期鼻咽癌(NPC)的治疗效果并不理想。在这里,我们开发了一种叶酸(FA)修饰、吉非替尼(GEF)和钇 90(Y90)共载、核壳结构的脂质-聚合物杂化纳米粒(FA-GEF-Y90-LPNP)。研究了其粒径和 Zeta 电位、药物释放行为以及肿瘤细胞的摄取情况。在癌细胞和荷瘤小鼠中评估了 LPNP 的抗肿瘤效率和毒性。平均粒径为 150nm,Zeta 电位为-40mV 的 FA-GEF-Y90-LPNP 能够增强 NPC 细胞的积累,并表现出最高的细胞毒性。FA-GEF-Y90-LPNP 组的 AUC 和 T 分别为 217.62±10.32mg/L.h 和 12.09±0.43h。FA-GEF-Y90-LPNP 表现出最好的体内肿瘤抑制能力,导致第 21 天肿瘤体积为 221.2±13.5mm。FA-GEF-Y90-LPNP 治疗导致体重几乎没有差异。这可能表明 FA-GEF-Y90-LPNP 的全身毒性较低,可作为 NPC 治疗的安全系统。