用于顺铂靶向递送的叶酸修饰、负载吲哚菁绿的脂质-聚合物杂化纳米颗粒。
Folate-modified, indocyanine green-loaded lipid-polymer hybrid nanoparticles for targeted delivery of cisplatin.
作者信息
Gu Lianshuai, Shi Tianyi, Sun Yu, You Chaoqun, Wang Senlin, Wen Gaoju, Chen Lan, Zhang Xiangyang, Zhu Jin, Sun Baiwang
机构信息
a School of Chemistry and Chemical Engineering , Southeast University , Nanjing , China.
b School of Pharmacy , Wannan Medical College , Wuhu , China.
出版信息
J Biomater Sci Polym Ed. 2017 May;28(7):690-702. doi: 10.1080/09205063.2017.1296347. Epub 2017 Feb 23.
Cisplatin is a potent antitumor drug, which is widely applied in clinical cancer treatment. However, cisplatin can hardly distinguish between healthy tissue and tumor tissue, resulting in serious toxic side effects. Indocyanine green (ICG) is a FDA-approved near-infrared (NIR) fluorescence dye which has been used in photothermal therapy and optically mediated diagnostic, but the application of ICG is limited by its concentration-dependent aggregation, poor aqueous stability in vitro, lack of target specificity and rapid elimination from the body. Herein, to overcome these limitations of cisplatin and ICG, we fabricated folate-modified, cisplatin, ICG-loaded lipid-polymer hybrid nanoparticles (FCINPs) using a single-step sonication method. The FCINPs exhibited well-defined monodispersity, significant stability and excellent NIR penetration ability. The intracellular uptake experiment showed that the targeting efficacy of the FCINPs was more effective in folate receptors (FRs) over-expressing MCF-7 cells than FRs negative A549 cells. In addition, compared with chemo or photothermal treatment alone, the treatment of FCINPs in combination with 808 nm NIR laser irradiation can significantly induce the apoptosis and necrosis of MCF-7 cells. These findings indicated that the FCINPs would be a promising nanosized drug formulation for tumor-targeted therapy in the future.
顺铂是一种强效抗肿瘤药物,广泛应用于临床癌症治疗。然而,顺铂很难区分健康组织和肿瘤组织,会导致严重的毒副作用。吲哚菁绿(ICG)是一种经美国食品药品监督管理局(FDA)批准的近红外(NIR)荧光染料,已用于光热疗法和光学介导诊断,但ICG的应用受到其浓度依赖性聚集、体外水稳定性差、缺乏靶向特异性以及从体内快速清除的限制。在此,为克服顺铂和ICG的这些局限性,我们采用单步超声法制备了叶酸修饰的、负载顺铂和ICG的脂质-聚合物杂化纳米颗粒(FCINPs)。FCINPs表现出明确的单分散性、显著的稳定性和优异的近红外穿透能力。细胞内摄取实验表明,FCINPs在过表达叶酸受体(FRs)的MCF-7细胞中的靶向效果比FRs阴性的A549细胞更有效。此外,与单独的化疗或光热治疗相比,FCINPs联合808 nm近红外激光照射治疗可显著诱导MCF-7细胞凋亡和坏死。这些研究结果表明,FCINPs在未来将是一种有前景的用于肿瘤靶向治疗的纳米药物制剂。