Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy

Joseph M. Caster, Stephanie K. Yu, Artish N. Patel, Nicole J. Newman, Zachary J. Lee, Samuel B. Warner, Kyle T. Wagner, Kyle C. Roche, Xi Tian, Yuanzeng Min, Andrew Z. Wang

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1673-1683
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume13
Issue number5
DOIs
StatePublished - Jul 2017
Externally publishedYes

Keywords

  • Chemoradiotherapy
  • KU60019
  • Nanoparticle
  • Nanoparticle radiosensitization
  • Wortmannin

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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