Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, Telangana, India.
Department of Biotechnology and Bioinformatics, Yogi Vemana University, Kadapa, Andhra Pradesh, India.
Colloids Surf B Biointerfaces. 2020 Jul;191:110979. doi: 10.1016/j.colsurfb.2020.110979. Epub 2020 Mar 18.
Intriguing properties and structural dynamics of Lactoferrin have been exploited in numerous applications, including its use as self-assembling, pH sensitive nanoparticles to deliver intended cargo at the disease site. In this study, we explore the possibility of surface modification of Lactoferrin nanoparticles to hone its specificity to target HIV-1 infected cells. Existence of free cysteine groups on Lactoferrin nanoparticles available for reaction with external molecules facilitates conjugation on the surface with Sodium 2-mercaptoethanesulfonate (MES). Conjugation with MES is used to edge a negative charge that can mimic CCR5 and Heparan sulfate (initial point of contact of HIV-1 env to host cell surface) electrostatic charge (Sulfate group). A simple sono-chemical irradiation method was employed for self-assembly of Nanoparticles and for surface modification. The nanoparticles serve dual purpose to abrogate extracellular entry and to target viral enzymes, when loaded with ART drugs. The morphology and size distribution of the formed particles were explored using Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM) and Dynamic Light Scattering. Raman SERS was employed to understand the difference in the protein upon surface modification. The anti-HIV property of the particles was confirmed in-vitro. The modified device demonstrated acceptable nanoparticle properties with controlled release and higher effective concentration in the area of infection.
乳铁蛋白具有有趣的特性和结构动力学，已在许多应用中得到了利用，包括将其用作自组装、pH 敏感的纳米颗粒，以将预期的货物递送到疾病部位。在这项研究中，我们探索了对乳铁蛋白纳米颗粒进行表面修饰的可能性，以提高其对 HIV-1 感染细胞的靶向特异性。乳铁蛋白纳米颗粒上存在的游离半胱氨酸基团可与外部分子发生反应，有利于与 Sodium 2-mercaptoethanesulfonate (MES) 在表面上进行缀合。与 MES 的缀合产生负电荷，可模拟 CCR5 和硫酸乙酰肝素 (HIV-1 env 与宿主细胞表面最初接触点) 的静电电荷 (硫酸盐基团)。采用简单的超声化学辐射法实现纳米颗粒的自组装和表面修饰。当负载 ART 药物时，这些纳米颗粒具有双重作用，可以阻止细胞外进入，并靶向病毒酶。使用透射电子显微镜 (TEM)、扫描电子显微镜 (SEM) 和动态光散射研究了形成的颗粒的形态和尺寸分布。拉曼 SERS 用于了解表面修饰后蛋白质的差异。在体外证实了该颗粒的抗 HIV 特性。修饰后的设备具有可接受的纳米颗粒特性，在感染区域具有可控释放和更高的有效浓度。
