TY - JOUR
T1 - Nanoemulsion-Based Delivery of Fluorescent PARP Inhibitors in Mouse Models of Small Cell Lung Cancer
AU - Gonzales, Junior
AU - Kossatz, Susanne
AU - Roberts, Sheryl
AU - Pirovano, Giacomo
AU - Brand, Christian
AU - Pérez-Medina, Carlos
AU - Donabedian, Patrick
AU - de la Cruz, M. Jason
AU - Mulder, Willem J. M.
AU - Reiner, Thomas
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85056528630&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30354077
U2 - https://doi.org/10.1021/acs.bioconjchem.8b00640
DO - https://doi.org/10.1021/acs.bioconjchem.8b00640
M3 - Article
C2 - 30354077
SN - 1043-1802
VL - 29
SP - 3776
EP - 3782
JO - Bioconjugate chemistry
JF - Bioconjugate chemistry
IS - 11
ER -