Department of Pharmaceutical Sciences, University of Modena and RE, Modena, Italy.
Biomaterials. 2010 Apr;31(12):3395-403. doi: 10.1016/j.biomaterials.2010.01.049. Epub 2010 Feb 4.
There is a broad interest in the development of nanoparticles (NPs) carrying on their surface carbohydrates such as sialic acids. It is known that these carbohydrates influence the biological and physical properties of biopharmaceutical proteins and living cells. Macromolecular compounds containing these carbohydrates showed an anti-recognition effect, exert an antiviral effect and also are able to be recognized by the cell surface of some kind of cancer cells. Thus, in the present research we performed two different approaches in order to obtain polymeric (poly(D,L-lactide-co-glycolide), PLGA) NPs surface decorated with the sialic acid N-acetylneuraminic acid (Neu5Ac). The first strategy that has been followed is based on the derivatization of the polyester PLGA with the thioderivative of Neu5Ac, starting material for the preparation of the NPs; the second is based on the synthesis of compounds potentially able to insert their lipophilic moiety into the underivatized PLGA NPs during their preparation, and to display their hydrophilic moiety (Neu5Ac) on their surface. The first approach allowed the obtainment of NPs surface decorated with Neu5Ac, as evidenced by ESCA spectroscopy and interaction with the lectin Wheat Germ Agglutinin. Moreover, a formulation of these NPs suitable for in vitro assays showed that they are phagocytosed by human monocytes with an apparently different mechanism with respect of those made of underivatized PLGA. The second strategy led to NPs in which their surface appears to be very different with respect to the NPs obtained following the first strategy, with the carboxylic groups of Neu5Ac markedly shielded. Thus, the new Neu5Ac-modified PLGA polyester represent a useful starting material for the preparation of NPs surface decorated with this sialic acid.
人们对表面携带碳水化合物（如唾液酸）的纳米颗粒（NPs）的开发有着广泛的兴趣。已知这些碳水化合物会影响生物制药蛋白和活细胞的生物和物理特性。含有这些碳水化合物的大分子化合物表现出抗识别效应，发挥抗病毒作用，并且能够被某些癌细胞的细胞表面识别。因此，在目前的研究中，我们采用了两种不同的方法来获得表面带有唾液酸 N-乙酰神经氨酸（Neu5Ac）的聚合物（聚（D，L-丙交酯-共-乙交酯），PLGA） NPs。我们所遵循的第一个策略是基于聚酯 PLGA 与 Neu5Ac 的硫代衍生物的衍生化，这是制备 NPs 的起始原料；第二个策略是基于合成潜在的化合物，这些化合物能够在制备过程中插入其亲脂部分进入未衍生的 PLGA NPs，并在其表面展示其亲水部分（Neu5Ac）。第一种方法允许获得表面带有 Neu5Ac 的 NPs，这可以通过 ESCA 光谱和与麦胚凝集素的相互作用来证明。此外，这些 NPs 的一种适合于体外试验的制剂表明，它们被人单核细胞吞噬，其机制与由未衍生的 PLGA 制成的 NPs 明显不同。第二种策略导致 NPs 的表面看起来与第一种策略得到的 NPs 非常不同，Neu5Ac 的羧酸基团明显被屏蔽。因此，新的 Neu5Ac 修饰的 PLGA 聚酯代表了一种有用的起始原料，可用于制备表面带有这种唾液酸的 NPs。
