Institut National de la Santé et de la Recherche Médicale, INSERM U779, Le Kremlin-Bicêtre, France.
Biomaterials. 2010 Aug;31(23):6069-74. doi: 10.1016/j.biomaterials.2010.04.039. Epub 2010 May 20.
Biomimetic nanoparticles based on polysaccharides-poly(alkylcyanoacrylates) copolymers were initially developed in view of drug delivery. Core-shell nanoparticles covered with a sufficiently long brush of polysaccharides were shown to be very low complement activators and have the potential for long circulation times in the bloodstream. Such nanoparticles bearing haemoglobin were envisaged as potential red cell substitutes. Different core-shell nanoparticles with a brush shell made of dextran, dextran-sulphate, or heparin were prepared and haemoglobin (Hb) could be adsorbed on their surface. Benzene tetracarboxylic acid (BTCA) was used as a coupling agent for Hb to dextran-coated nanoparticles; the Hb loading capacity of the dextran nanoparticles showed a 9.3 fold increased. The coupled Hb maintained the allosteric properties of free Hb. While modification of nanoparticles by BTCA slightly increased complement activation, the further addition of Hb totally reversed this effect providing Hb-loaded nanoparticles with a very low level of complement activation. Such nanoparticles could be a suitable alternative to haemoglobin solutions in the development of a blood substitute.
基于多糖-聚(烷基氰基丙烯酸酯)共聚物的仿生纳米粒子最初是为药物输送而开发的。具有足够长多糖刷的核壳纳米粒子被证明是非常低的补体激活物,并具有在血液中长循环时间的潜力。携带血红蛋白的此类纳米粒子被设想为潜在的红细胞替代品。用葡聚糖、葡聚糖硫酸盐或肝素制成的刷壳的不同核壳纳米粒子被制备,并且血红蛋白(Hb)可以吸附在其表面上。苯四羧酸(BTCA)被用作连接剂将 Hb 连接到葡聚糖涂覆的纳米粒子上;葡聚糖纳米粒子的 Hb 负载能力增加了 9.3 倍。连接的 Hb 保持了游离 Hb 的变构特性。虽然 BTCA 对纳米粒子的修饰略微增加了补体激活,但进一步添加 Hb 完全逆转了这种效应,使负载 Hb 的纳米粒子具有非常低的补体激活水平。此类纳米粒子可能是血红蛋白溶液在血液替代品开发中的合适替代品。