کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5033177 | 1370008 | 2017 | 11 صفحه PDF | دانلود رایگان |
Nanoparticle (NP) chemotherapeutics 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 toward 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.
Graphical AbstractSub-50Â 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.181
Journal: Nanomedicine: Nanotechnology, Biology and Medicine - Volume 13, Issue 5, July 2017, Pages 1673-1683