摘要
Multi-drug delivery focuses on different signaling pathways in cancer cells and has synergistic antiproliferative effects.In this manuscript,we developed folic acid(FA)-conjugated polymeric multi-drug nanoparticles(FA-PMDNPs)consisting of poly-L-lysine(PLL)and poly glutamic-conjugated PTX/GEM(PGA-PTX and PGA-GEM)for FA receptor-targeted synergistic breast cancer therapy.The carboxyl-rich structure of PGA provided plenty reaction sites and negative charge for drug loading.Transmission electron microscopy(TEM)results showed that FA-PMDNPs had uniform particle size and spherical morphology.The hemolysis study proved that FA-PMDNPs had good biocompatibility.In vitro cell viability and in vivo studies showed that FA-PMDNPs more effectively inhibited the proliferation of FA receptor(FR)-overexpressing breast cancer cells(4T1)than the pure drugs.Consequently,these results demonstrated that FA-PMDNPs could be effectively targeted at cancer cells compared with free drugs,indicating their strong potential as efficient multi-drug-carrying nano-platforms for cancer treatment.
针对肿瘤细胞不同信号通路的多药递药系统具有协同治疗的作用。本文中,我们开发了一种由聚-L-赖氨酸(PLL)和负载有紫杉醇/吉西他滨的聚谷氨酸(PGA-PTX和PGA-GEM)组装的叶酸(FA)修饰的聚合物多药纳米粒(FA-PMDNPs),用于FA受体靶向的乳腺癌协同治疗。PGA富含大量的羧基,为药物负载提供了充足的反应位点和负电荷。透射电子显微镜(TEM)结果表明制备的FA-PMDNPs粒径均一,为球形。溶血实验表明FA-PMDNP具有良好的生物相容性。由于乳腺癌细胞(4T1)的FA受体(FR)高表达,体外细胞活性和体内疗效结果表明FA-PMDNP比单药能够更有效地抑制乳腺癌细胞(4T1)的增殖。与单药相比,FA-PMDNPs可以有效地靶向癌细胞。因此,FA受体靶向双重载药递药系统是一种具有潜力的肿瘤纳米治疗平台。
基金
National Natural Science Foundation of China(Grant No.21877061)
Natural Science Foundation of Jiangsu Province(Grant No.BK20171448)
National and Local Joint Engineering Research Center of Biomedical Functional Materials。
