Shah Neha B, Vercellotti Gregory M, White James G, Fegan Adrian, Wagner Carston R, Bischof John C
Department of Biomedical Engineering, ‡Department of Medicine, §Department of Lab Medicine and Pathology, ∥Department of Medicinal Chemistry, ⊥Department of Mechanical Engineering, and #Department of Urologic Surgery, University of Minnesota , Minneapolis, Minnesota 55455, United States.
Mol Pharm. 2012 Aug 6;9(8):2146-55. doi: 10.1021/mp200626j. Epub 2012 Jul 23.
Theranostic nanoparticles (NPs) cannot reach their target tissue without first passing through blood; however, the influence of blood protein and blood cell interactions on NP biodistribution are not well understood. The current work shows that 30 nm PEGylated gold NPs (GNPs) interact not only with blood proteins as thought before but also with blood cells (especially platelets and monocytes) in vivo and that longer blood circulation correlates strongly with tumor uptake. Further, GNP surface properties such as negative charge or lyophilization had either a minimal (i.e., charge) or 15-fold increase (i.e., fresh vs lyophilized) in blood retention times and tumor uptake. Tumor accumulation was increased over 10-fold by use of a bioactive ligand (i.e., TNF) on the lyophilized GNP surface. Resident macrophages were primarily responsible for the bulk of GNP uptake in liver while spleen uptake was highly surface property dependent and appears to involve macrophages and cellular interaction between the red and white pulp. This study shows that the PEG layer and ligand on the surface of the NP are critical to blood interactions and eventual tumor and RES organ biodistribution in vivo.
诊疗纳米颗粒（NPs）在未首先穿过血液的情况下无法到达其靶组织；然而，血液蛋白和血细胞相互作用对NP生物分布的影响尚未得到充分理解。目前的研究表明，30纳米的聚乙二醇化金纳米颗粒（GNPs）不仅如之前所认为的那样与血液蛋白相互作用，而且在体内还与血细胞（尤其是血小板和单核细胞）相互作用，并且更长的血液循环时间与肿瘤摄取密切相关。此外，GNP的表面性质，如负电荷或冻干，对血液保留时间和肿瘤摄取的影响要么极小（即电荷），要么增加15倍（即新鲜与冻干相比）。通过在冻干的GNP表面使用生物活性配体（即TNF），肿瘤积累增加了10倍以上。驻留巨噬细胞主要负责肝脏中大部分GNP的摄取，而脾脏摄取高度依赖表面性质，似乎涉及巨噬细胞以及红髓和白髓之间的细胞相互作用。这项研究表明，NP表面的聚乙二醇层和配体对于体内血液相互作用以及最终的肿瘤和RES器官生物分布至关重要。
