Nanoemulsion-based delivery of fluorescent PARP inhibitors in mouse models of small cell lung cancer Journal Article


Authors: Gonzales, J.; Kossatz, S.; Roberts, S.; Pirovano, G.; Brand, C.; Pérez-Medina, C.; Donabedian, P.; De La Cruz, M. J.; Mulder, W. J. M.; Reiner, T.
Article Title: Nanoemulsion-based delivery of fluorescent PARP inhibitors in mouse models of small cell lung cancer
Abstract: The preclinical potential of many diagnostic and therapeutic small molecules is limited by their rapid washout kinetics and consequently modest pharmacological performances. In several cases, these could be improved by loading the small molecules into nanoparticulates, improving blood half-life, in vivo uptake and overall pharmacodynamics. In this study, we report a nanoemulsion (NE) encapsulated form of PARPi-FL. As a proof of concept, we used PARPi-FL, which is a fluorescently labeled sensor for olaparib, a FDA-approved small molecule inhibitor of the nuclear enzyme poly(ADP-ribose)polymerase 1 (PARP1). Encapsulated PARPi-FL showed increased blood half-life, and delineated subcutaneous xenografts of small cell lung cancer (SCLC), a fast-progressing disease where efficient treatment options remain an unmet clinical need. Our study demonstrates an effective method for expanding the circulation time of a fluorescent PARP inhibitor, highlighting the pharmacokinetic benefits of nanoemulsions as nanocarriers and confirming the value of PARPi-FL as an imaging agent targeting PARP1 in small cell lung cancer. Copyright © 2018 American Chemical Society.
Journal Title: Bioconjugate Chemistry
Volume: 29
Issue: 11
ISSN: 1043-1802
Publisher: American Chemical Society  
Date Published: 2018-11-21
Start Page: 3776
End Page: 3782
Language: English
DOI: 10.1021/acs.bioconjchem.8b00640
PUBMED: 30354077
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
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