High Payload Dual Therapeutic-Imaging Nanocarriers for Triggered Tumor Deliveryopen access
- Authors
- Kim, Jin-Ki; Yuan, Hong; Nie, Jingxin; Yang, Yu-Tsai; Leggas, Markos; Potter, Philip M.; Rinehart, John; Jay, Michael; Lu, Xiuling
- Issue Date
- Sep-2012
- Publisher
- WILEY-V C H VERLAG GMBH
- Keywords
- nanoparticles; dexamethasone; ester prodrug; triggered release; SPECT; CT imaging
- Citation
- SMALL, v.8, no.18, pp.2895 - 2903
- Indexed
- SCIE
SCOPUS
- Journal Title
- SMALL
- Volume
- 8
- Number
- 18
- Start Page
- 2895
- End Page
- 2903
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/31836
- DOI
- 10.1002/smll.201200437
- ISSN
- 1613-6810
- 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 Es1e(-/-)/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.
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