Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile, Santiago, Chile.
Int J Nanomedicine. 2020 Mar 17;15:1837-1851. doi: 10.2147/IJN.S237820. eCollection 2020.
Gold nanorods are highly reactive, have a large surface-to-volume ratio, and can be functionalized with biomolecules. Gold nanorods can absorb infrared electromagnetic radiation, which is subsequently dispersed as local heat. Gold nanoparticles can be used as powerful tools for the diagnosis and therapy of different diseases. To improve the biological barrier permeation of nanoparticles with low cytotoxicity, in this study, we conjugated gold nanorods with cell-penetrating peptides (oligoarginines) and with the amphipathic peptide CLPFFD.
We studied the interaction of the functionalized gold nanorods with biological membrane models (liposomes) by dynamic light scattering, transmission electron microscopy and the Langmuir balance. Furthermore, we evaluated the effects on cell viability and permeability with an MTS assay and TEM.
The interaction study by DLS, the Langmuir balance and cryo-TEM support that GNR-ArgCLPFFD enhances the interactions between GNRs and biological membranes. In addition, cells treated with GNR-ArgCLPFFD internalized 80% more nanoparticles than cells treated with GNR alone and did not induce cell damage.
Our results indicate that incorporation of an amphipathic sequence into oligoarginines for the functionalization of gold nanorods enhances biological membrane nanoparticle interactions and nanoparticle cell permeability with respect to nanorods functionalized with oligoarginine. Overall, functionalized gold nanorods with amphipathic arginine rich peptides might be candidates for improving drug delivery by facilitating biological barrier permeation.
金纳米棒具有高反应性、大的表面积与体积比,并且可以与生物分子进行功能化。金纳米棒可以吸收红外电磁辐射,随后将其分散为局部热量。金纳米粒子可用作诊断和治疗不同疾病的有力工具。为了提高具有低细胞毒性的纳米粒子的生物屏障渗透能力,在本研究中,我们将金纳米棒与穿透肽(寡精氨酸)和两亲肽 CLPFFD 进行了缀合。
我们通过动态光散射、透射电子显微镜和 Langmuir 天平研究了功能化金纳米棒与生物膜模型(脂质体)的相互作用。此外,我们通过 MTS 测定和 TEM 评估了对细胞活力和通透性的影响。
DLS、Langmuir 天平以及冷冻 TEM 的相互作用研究表明,GNR-ArgCLPFFD 增强了 GNR 与生物膜之间的相互作用。此外,与单独用 GNR 处理的细胞相比,用 GNR-ArgCLPFFD 处理的细胞内化了 80%更多的纳米颗粒,并且不会诱导细胞损伤。
我们的结果表明,将两亲性序列掺入寡精氨酸中用于金纳米棒的功能化,可增强生物膜纳米颗粒相互作用以及纳米颗粒的细胞通透性,而用寡精氨酸功能化的纳米棒则没有。总的来说,具有两亲性富含精氨酸的肽的功能化金纳米棒可能是通过促进生物屏障渗透来改善药物递送的候选物。