Fluorocoxib A loaded nanoparticles enable targeted visualization of cyclooxygenase-2 in inflammation and cancer.

Uddin MJ, Werfel TA, Crews BC, Gupta MK, Kavanaugh TE, Kingsley PJ, Boyd K, Marnett LJ, Duvall CL
Biomaterials. 2016 92: 71-80

PMID: 27043768 · PMCID: PMC4833621 · DOI:10.1016/j.biomaterials.2016.03.028

Cyclooxygenase-2 (COX-2) is expressed in virtually all solid tumors and its overexpression is a hallmark of inflammation. Thus, it is a potentially powerful biomarker for the early clinical detection of inflammatory disease and human cancers. We report a reactive oxygen species (ROS) responsive micellar nanoparticle, PPS-b-POEGA, that solubilizes the first fluorescent COX-2-selective inhibitor fluorocoxib A (FA) for COX-2 visualization in vivo. Pharmacokinetics and biodistribution of FA-PPS-b-POEGA nanoparticles (FA-NPs) were assessed after a fully-aqueous intravenous (i.v.) administration in wild-type mice and revealed 4-8 h post-injection as an optimal fluorescent imaging window. Carrageenan-induced inflammation in the rat and mouse footpads and 1483 HNSCC tumor xenografts were successfully visualized by FA-NPs with fluorescence up to 10-fold higher than that of normal tissues. The targeted binding of the FA cargo was blocked by pretreatment with the COX-2 inhibitor indomethacin, confirming COX-2-specific binding and local retention of FA at pathological sites. Our collective data indicate that FA-NPs are the first i.v.-ready FA formulation, provide high signal-to-noise in inflamed, premalignant, and malignant tissues, and will uniquely enable clinical translation of the poorly water-soluble FA compound.

Copyright © 2016 Elsevier Ltd. All rights reserved.

MeSH Terms (17)

Animals Cell Line, Tumor Cyclooxygenase 2 Dynamic Light Scattering Female Humans Indoles Inflammation Injections, Intraperitoneal Mice, Inbred C57BL Mice, Nude Molecular Imaging Nanoparticles Neoplasms Polymers Rhodamines Tissue Distribution

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