期刊
BIOCONJUGATE CHEMISTRY
卷 29, 期 11, 页码 3776-3782出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.bioconjchem.8b00640
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- Memorial Sloan Kettering Cancer Center's Animal Imaging Core Facility and Molecular Imaging Probes Core Facility
- National Institutes of Health [P30 CA008748, R01 HL125703, R01 CA204441, K99 CA218875, R01 CA204441-03S1]
- Memorial Sloan Kettering Cancer Center's Nuclear Magnetic Resonance Analytical Core Facility
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.
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