Protonated nanoparticle surface governing ligand tethering and cellular targeting.
Protonated nanoparticle surface governing ligand tethering and cellular targeting.
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DOI：
10.1021/nn9000148
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发表时间：
2009-05-26
期刊：
影响因子：
17.1
通讯作者：
Seal, Sudipta
中科院分区：
文献类型：
--
作者：
Vincent, Abhilash;Babu, Suresh;Heckert, Eric;Dowding, Janet;Hirst, Suzanne M.;Inerbaev, Talgat M.;Self, William T.;Reilly, Christopher M.;Masunov, Artem E.;Rahman, Talat S.;Seal, Sudipta
关键词：
纳米粒子由于其微小的尺寸和穿透细胞膜的能力，在有效药物输送方面显示出巨大的潜力。纳米粒子的细胞靶向通常是通过表面修饰和配基连接来实现的。然而，纳米颗粒到达靶细胞并内化的效率取决于靶向配体的稳定性和配体纳米颗粒结合的化学性质。纳米生物材料研究的最新进展已经证明了氧化铈纳米颗粒(CNPs)在保护细胞免受氧化应激方面具有超氧化物歧化酶(SOD)模拟活性。CNPs具有良好的生物相容性，可作为药物载体向肿瘤部位转运和释放药物。在这里，我们结合单分子力谱(SMFS)和密度泛函理论(DFT)模拟来了解转铁蛋白(一种在癌细胞中过度表达的配体蛋白)与CNPs之间的相互作用。SMFS研究表明，随着CNP的正Zeta电位的增加，转铁蛋白与纳米颗粒表面的粘附性增加。密度泛函理论计算得到的结合能值预测，经过表面质子化和电荷修饰后，转铁蛋白和CNP之间的结合强度会增加。将转铁蛋白偶联的CNPs与人肺癌细胞(A549)和正常胚肺细胞(WI-38)孵育，检测其结合稳定性和细胞摄取效率。结果表明，调整纳米颗粒的表面性质对于更好的配体吸附和细胞摄取具有重要意义。
Nanoparticles have shown tremendous potential for effective drug delivery due to their tiny size and cell membrane penetration capabilities. Cellular targeting with nanoparticles is often achieved by surface modifications followed by ligand conjugation. However, the efficiency of the nanoparticles reaching the target cells and getting internalized depends on the stability of targeting ligands and the chemical nature of the ligand nanoparticle binding. Recent advancements in nanobiomaterials research have proven the superoxide dismutase (SOD) mimetic activity of cerium oxide nanoparticles (CNPs) in protecting cells against oxidative stress. Due to their excellent biocompatibility, CNPs can be used as potential drug carrier that can transport and release drugs to the malignant sites. Here we combine single molecule force spectroscopy (SMFS) and density functional theory (DFT) simulations to understand the interaction between transferrin, a ligand protein over-expressed in cancer cells, and CNPs. SMFS studies demonstrate an increase in the transferrin adhesion to the nanoparticles surface with an increase in positive zeta potential of CNPs. Binding energy values obtained from DFT calculations predict an increase in bond strength between the transferrin and CNPs upon surface protonation and charge modification. Transferrin conjugated CNPs were tested for their binding stability and preferential cellular uptake efficiency by incubating them with human lung cancer cells (A549) and normal embryo lung cells (WI-38). The results demonstrate the importance of tuning the surface properties of nanoparticles for better ligand adsorption and cellular uptake.
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影响因子：
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作者：
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通讯作者：
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