Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy.
Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy.
复制标题
DOI：
10.1016/j.nano.2017.03.002
复制
发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Wang AZ
中科院分区：
文献类型：
--
作者：
Caster JM;Yu SK;Patel AN;Newman NJ;Lee ZJ;Warner SB;Wagner KT;Roche KC;Tian X;Min Y;Wang AZ
纳米粒子（NP）治疗可以提高放化疗（CRT）的治疗指数。然而，NP的物理性质，如粒度，对CRT的影响是未知的。为了解决这个问题，我们研究了NP大小对CRT中生物分布、疗效和毒性的影响。配制包封渥曼青霉素（wtmn）或KU 50019的PEG-PLGA NP（50、100、150 nm平均直径）。这些NP制剂在体外对HT 29、SW 480和lovo直肠癌细胞系是有效的放射增敏剂。在体内，最小的颗粒避免了肝脏和脾脏的积累，同时比较大的颗粒更均匀地穿透肿瘤异种移植物。然而，较小的颗粒在体内并不更有效。相反，存在使用中等尺寸NP增强功效的趋势。最小的KU60019颗粒比较大的颗粒引起更多的小肠毒性。我们的研究结果表明，颗粒大小显着影响纳米治疗剂的生物分布和毒性，但不支持较小颗粒更适合这种临床应用的结论。亚50 nm的载药纳米颗粒避免了肝脏清除，并更均匀地分布在肿瘤内。然而，它们并不更有效，并且与较大颗粒相比具有更多的小肠毒性。
Nanoparticle (NP) therapeutics can improve the therapeutic index of chemoradiotherapy (CRT). However, the effect of NP physical properties, such particle size, on CRT is unknown. To address this, we examined the effects of NP size on biodistribution, efficacy and toxicity in CRT. PEG-PLGA NPs (50, 100, 150 nm mean diameters) encapsulating wotrmannin (wtmn) or KU50019 were formulated. These NP formulations were potent radiosensitizers in vitro in HT29, SW480, and lovo rectal cancer lines. In vivo, the smallest particles avoided hepatic and splenic accumulation while more homogeneously penetrating tumor xenografts than larger particles. However, smaller particles were no more effective in vivo. Instead, there was a trend towards enhanced efficacy with medium sized NPs. The smallest KU60019 particles caused more small bowel toxicity than larger particles. Our results showed that particle size significantly affects nanotherapeutics' biodistrubtion and toxicity but does not support the conclusion that smaller particles are better for this clinical application. Sub50 nm drug-loaded NPs avoid hepatic clearance and more homogeneously distribute within tumors. However, they are no more efficacious and are associated with more small bowel toxicity than larger particles.