ABSTRACT
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.
Subject(s)
Chemoradiotherapy , Nanoparticles , Androstadienes/pharmacokinetics , Animals , Heterografts , Humans , Mice , Particle Size , Polymers , Rectal Neoplasms , Tissue Distribution , WortmanninABSTRACT
Nanomedicine is a relatively new field that is rapidly evolving. Formulation of drugs on the nanoscale imparts many physical and biological advantages. Such advantages can in turn translate into improved therapeutic efficacy and reduced toxicity. While approximately 50 nanotherapeutics have already entered clinical practice, a greater number of drugs are undergoing clinical investigation for a variety of indications. This review aims to examine all the nanoformulations that are currently undergoing clinical investigation and their outlook for ultimate clinical translation. WIREs Nanomed Nanobiotechnol 2017, 9:e1416. doi: 10.1002/wnan.1416 For further resources related to this article, please visit the WIREs website.
