England Christopher G, Huang Justin S, James Kurtis T, Zhang Guandong, Gobin André M, Frieboes Hermann B
Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, United States of America; James Graham Brown Cancer Center, University of Louisville, Louisville, KY, United States of America.
Department of Medicine, University of Louisville, Louisville, KY, United States of America.
PLoS One. 2015 Jun 5;10(6):e0129172. doi: 10.1371/journal.pone.0129172. eCollection 2015.
Nanoparticle uptake and distribution to solid tumors are limited by reticuloendothelial system systemic filtering and transport limitations induced by irregular intra-tumoral vascularization. Although vascular enhanced permeability and retention can aid targeting, high interstitial fluid pressure and dense extracellular matrix may hinder local penetration. Extravascular diffusivity depends upon nanoparticle size, surface modifications, and tissue vascularization. Gold nanoparticles functionalized with biologically-compatible layers may achieve improved uptake and distribution while enabling cytotoxicity through synergistic combination of chemotherapy and thermal ablation. Evaluation of nanoparticle uptake in vivo remains difficult, as detection methods are limited. We employ hyperspectral imaging of histology sections to analyze uptake and distribution of phosphatidylcholine-coated citrate gold nanoparticles (CGN) and silica-gold nanoshells (SGN) after tail-vein injection in mice bearing orthotopic pancreatic adenocarcinoma. For CGN, the liver and tumor showed 26.5 ± 8.2 and 23.3 ± 4.1 particles/100 μm2 within 10 μm from the nearest source and few nanoparticles beyond 50 μm, respectively. The spleen had 35.5 ± 9.3 particles/100 μm2 within 10 μm with penetration also limited to 50 μm. For SGN, the liver showed 31.1 ± 4.1 particles/100 μm2 within 10 μm of the nearest source with penetration hindered beyond 30 μm. The spleen and tumor showed uptake of 22.1 ± 6.2 and 15.8 ± 6.1 particles/100 μm2 within 10 μm, respectively, with penetration similarly hindered. CGH average concentration (nanoparticles/μm2) was 1.09 ± 0.14 in the liver, 0.74 ± 0.12 in the spleen, and 0.43 ± 0.07 in the tumor. SGN average concentration (nanoparticles/μm2) was 0.43 ± 0.07 in the liver, 0.30 ± 0.06 in the spleen, and 0.20 ± 0.04 in the tumor. Hyperspectral imaging of histology sections enables analysis of phosphatidylcholine-coated gold-based nanoparticles in pancreatic tumors with the goal to improve nanotherapeutic efficacy.
纳米颗粒对实体瘤的摄取和分布受到网状内皮系统全身过滤以及肿瘤内不规则血管化所导致的转运限制。尽管血管的高通透性和滞留效应有助于靶向作用，但高组织间液压力和致密的细胞外基质可能会阻碍局部渗透。血管外扩散率取决于纳米颗粒的大小、表面修饰以及组织血管化情况。用生物相容性层功能化的金纳米颗粒可能会实现更好的摄取和分布，同时通过化疗与热消融的协同组合实现细胞毒性。由于检测方法有限，体内纳米颗粒摄取的评估仍然困难。我们采用组织学切片的高光谱成像来分析在患有原位胰腺腺癌的小鼠尾静脉注射磷脂酰胆碱包被的柠檬酸盐金纳米颗粒（CGN）和二氧化硅 - 金纳米壳（SGN）后的摄取和分布情况。对于CGN，在距离最近来源10μm范围内，肝脏和肿瘤分别显示26.5±8.2和23.3±4.1个颗粒/100μm²，而在50μm以外几乎没有纳米颗粒。脾脏在10μm范围内有35.5±9.3个颗粒/100μm²，渗透也限于50μm。对于SGN，在距离最近来源10μm范围内，肝脏显示31.1±4.1个颗粒/100μm²，在30μm以外渗透受阻。脾脏和肿瘤在10μm范围内分别显示摄取22.1±6.2和15.8±6.1个颗粒/100μm²，渗透同样受阻。CGN在肝脏中的平均浓度（纳米颗粒/μm²）为1.09±0.14，在脾脏中为0.74±0.12，在肿瘤中为0.43±0.07。SGN在肝脏中的平均浓度（纳米颗粒/μm²）为0.43±0.07，在脾脏中为0.30±0.06，在肿瘤中为0.20±0.04。组织学切片的高光谱成像能够分析胰腺肿瘤中磷脂酰胆碱包被的金基纳米颗粒，目标是提高纳米治疗效果。
