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Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner

Affiliation
Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
Evans, Angela C.;
Affiliation
Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
Martin, Kelly A.;
ORCID
0000-0002-0281-4222
Affiliation
Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
Saxena, Manoj;
Affiliation
Institute of Radiation Medicine, Helmholtz Zentrum München, 85764 Munich, Germany
Bicher, Sandra;
Affiliation
Engineering Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
Wheeler, Elizabeth;
ORCID
0000-0002-7556-3137
Affiliation
National Institute of Genomic Medicine, Oncogenomic Consortium, Mexico City 14610, Mexico
Cordova, Emilio J.;
Affiliation
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
Porada, Christopher D.;
Affiliation
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
Almeida-Porada, Graça;
ORCID
0000-0002-6263-600X
Affiliation
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA
Kato, Takamitsu A.;
Affiliation
Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
Wilson, Paul F.;
ORCID
0000-0003-1389-4018
Affiliation
Department of Radiation Oncology, University of California Davis, Sacramento, CA 95817, USA
Coleman, Matthew A.

Curcumin, a natural polyphenol derived from the spice turmeric ( Curcuma longa ), contains antioxidant, anti-inflammatory, and anti-cancer properties. However, curcumin bioavailability is inherently low due to poor water solubility and rapid metabolism. Here, we further refined for use curcumin incorporated into “biomimetic” nanolipoprotein particles (cNLPs) consisting of a phospholipid bilayer surrounded by apolipoprotein A1 and amphipathic polymer scaffolding moieties. Our cNLP formulation improves the water solubility of curcumin over 30-fold and produces nanoparticles with ~350 µg/mL total loading capacity for downstream in vitro and in vivo applications. We found that cNLPs were well tolerated in AG05965/MRC-5 human primary lung fibroblasts compared to cultures treated with curcumin solubilized in DMSO (curDMSO). Pre-treatment with cNLPs of quiescent G0/G1-phase MRC-5 cultures improved cell survival following 137 Cs gamma ray irradiations, although this finding was reversed in asynchronously cycling log-phase cell cultures. These findings may be useful for establishing cNLPs as a method to improve curcumin bioavailability for administration as a radioprotective and/or radiomitigative agent against ionizing radiation (IR) exposures in non-cycling cells or as a radiosensitizing agent for actively dividing cell populations, such as tumors.

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