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High Payload Dual Therapeutic‐Imaging Nanocarriers for Triggered Tumor Delivery
Author(s) -
Kim JinKi,
Yuan Hong,
Nie Jingxin,
Yang YuTsai,
Leggas Markos,
Potter Philip M.,
Rinehart John,
Jay Michael,
Lu Xiuling
Publication year - 2012
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201200437
Subject(s) - nanocarriers , in vivo , dexamethasone , drug delivery , in vitro , liver tumor , chemistry , pharmacology , esterase , cancer research , endocrinology , biology , biochemistry , enzyme , hepatocellular carcinoma , microbiology and biotechnology , organic chemistry
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 111 In, a signaling agent, is described. These NPs are uniform in size and composition. Single photon emission computed tomography imaging demonstrates significant tumor uptake of 111 In‐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 Es 1 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.