High payload dual therapeutic-imaging nanocarriers for triggered tumor delivery

Jin Ki Kim, Hong Yuan, Jingxin Nie, Yu Tsai Yang, Markos Leggas, Philip M. Potter, John Rinehart, Michael Jay, Xiuling Lu

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The in vitro and in vivo characterization of an optimized formulation of nanoparticles (NPs) loaded with a high content of dexamethasone palmitate (DEX-P), a chemotherapeutic adjuvant that decreases interstitial fluid pressure in tumors, and 111In, a signaling agent, is described. These NPs are uniform in size and composition. Single photon emission computed tomography imaging demonstrates significant tumor uptake of 111In-labeled DEX-P NPs in tumor-bearing mice. As with many nanoparticle-based drug delivery systems, significant liver accumulation is observed. Assessment of liver histology and blood tests show no apparent hepatic or renal toxicity of the DEX-P NPs. Conversion of DEX-P to DEX occurs when DEX-P NPs are incubated with mouse plasma, human tumor homogenate and ascites from tumor bearing mice, but not with human plasma. This conversion is slower in plasma from Es1 e(-/-)/SCID mice, a potential alternative animal model that better mimics humans; however, plasma from these mice are not completely devoid of esterase activity. The difference between blood and tumor esterase activity in humans facilitates the delivery of DEX-P NPs to tumors and the release of dexamethasone by an esterase trigger. Homogeneous dual therapeutic-imaging nanocarriers containing a chemotherapeutic adjuvant, dexamethasone palmitate (DEX-P), and a signaling agent, 111In, exhibit significant tumor uptake in single photon emission computed tomography images. High esterase activity in tumors, but not in human plasma, facilitates the esterolysis of the prodrug DEX-P resulting in the intra-tumoral release of DEX from DEX-P nanoparticles.

Original languageEnglish
Pages (from-to)2895-2903
Number of pages9
JournalSmall
Volume8
Issue number18
DOIs
StatePublished - Sep 24 2012

Keywords

  • SPECT/CT imaging
  • dexamethasone
  • ester prodrug
  • nanoparticles
  • triggered release

ASJC Scopus subject areas

  • General Chemistry
  • Engineering (miscellaneous)
  • Biotechnology
  • General Materials Science
  • Biomaterials

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