Department of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Biomaterials. 2012 Jan;33(1):256-69. doi: 10.1016/j.biomaterials.2011.09.028. Epub 2011 Oct 5.
Limitations to adenovirus infectivity can be overcome by association with magnetic nanoparticles and enforced infection by magnetic field influence. Here we examined three core-shell-type iron oxide magnetic nanoparticles differing in their surface coatings, particle sizes and magnetic properties for their ability to enhance the oncolytic potency of adenovirus Ad520 and to stabilize it against the inhibitory effects of serum or a neutralizing antibody. It was found that the physicochemical properties of magnetic nanoparticles are critical determinants of the properties which govern the oncolytic productivities of their complexes with Ad520. Although high serum concentration during infection or a neutralizing antibody had strong inhibitory influence on the uptake or oncolytic productivity of the naked virus, one particle type was identified which conferred high protection against both inhibitory factors while enhancing the oncolytic productivity of the internalized virus. This particle type equipped with a silica coating and adsorbed polyethylenimine, displaying a high magnetic moment and high saturation magnetization, mediated a 50% reduction of tumor growth rate versus control upon intratumoral injection of its complex with Ad520 and magnetic field influence, whereas Ad520 alone was inefficient. The correlations between physical properties of the magnetic particles or virus complexes and oncolytic potency are described herein.
通过与磁性纳米粒子结合，并通过磁场影响强制感染，可以克服腺病毒感染力的限制。在这里，我们研究了三种核壳型氧化铁磁性纳米粒子，它们在表面涂层、粒径和磁性能方面存在差异，以研究它们增强溶瘤腺病毒 Ad520 效力并抵抗血清或中和抗体抑制作用的能力。结果发现，磁性纳米粒子的物理化学性质是决定其与 Ad520 复合物的性质的关键因素，这些性质决定了其溶瘤生产力。虽然在感染过程中高浓度的血清或中和抗体对裸病毒的摄取或溶瘤生产力有很强的抑制作用，但有一种粒子类型被确定可以同时抵抗这两种抑制因素，同时增强内化病毒的溶瘤生产力。这种带有二氧化硅涂层和吸附聚乙烯亚胺的粒子类型，具有高磁矩和高饱和磁化强度，在肿瘤内注射其与 Ad520 的复合物并施加磁场影响后，可使肿瘤生长速率相对于对照组降低 50%，而单独使用 Ad520 则无效。本文描述了磁性粒子或病毒复合物的物理性质与溶瘤效力之间的相关性。
