Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Institute of Biomedical Engineering, Boğaziçi University, 34684 Çengelköy, Istanbul, Turkey.
ACS Appl Bio Mater. 2022 Feb 21;5(2):622-629. doi: 10.1021/acsabm.1c01090. Epub 2022 Jan 3.
Development of safer nanomedicines for drug delivery applications requires immense efforts to improve clinical outcomes. Targeting a specific cell, biocompatibility and biodegradability are vital properties of a nanoparticle to fulfill the safety criteria in medical applications. Herein, we fabricate antibody-functionalized carnauba wax nanoparticles encapsulated a hydrophobic drug mimetic, which is potentially interesting for clinical use due to the inert and nontoxic properties of natural waxes. The nanoparticles are synthesized applying miniemulsion methods by solidifying molten wax droplets and further evaporating the solvent from the dispersion. The pH-selective adsorption of antibodies (IgG1, immunoglobulin G1, and CD340, an antihuman HER2 antibody) onto the nanoparticle surface is performed for practical and effective functionalization, which assists to overcome the complexity in chemical modification of carnauba wax. The adsorption behavior of the antibodies is studied using isothermal titration calorimetry (ITC), which gives thermodynamic parameters including the enthalpy, association constant, and stoichiometry of the functionalization process. Both antibodies exhibit strong binding at pH 2.7. The CD340-decorated wax nanoparticles show specific cell interaction toward BT474 breast cancer cells and retain the targeting function even after 6 months of storage period.
为了改善临床效果,开发用于药物输送应用的更安全的纳米药物需要付出巨大的努力。靶向特定细胞、生物相容性和生物可降解性是纳米颗粒在医疗应用中满足安全标准的重要特性。在此,我们制备了抗体功能化巴西棕榈蜡纳米颗粒,封装了一种疏水性药物模拟物,由于天然蜡的惰性和无毒特性,它具有潜在的临床应用价值。纳米颗粒是通过固相反应用于微乳液方法来合成的熔融蜡液滴,并进一步从分散体中蒸发溶剂。为了进行实际有效的功能化,对抗体(IgG1、免疫球蛋白 G1 和 CD340,一种抗人 HER2 抗体)在纳米颗粒表面的 pH 选择性吸附进行了研究,这有助于克服巴西棕榈蜡化学修饰的复杂性。使用等温滴定量热法(ITC)研究了抗体的吸附行为,该方法提供了包括功能化过程的焓、结合常数和化学计量学在内的热力学参数。两种抗体在 pH 2.7 时均表现出强烈的结合。CD340 修饰的蜡纳米颗粒对 BT474 乳腺癌细胞表现出特异性的细胞相互作用,并且即使在 6 个月的储存期后仍保留靶向功能。