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

Abstract

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 137Cs 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.

Authors:
 [1];  [2]; ORCiD logo [3];  [4];  [2]; ORCiD logo [5];  [6];  [6]; ORCiD logo [7]; ORCiD logo [8]; ORCiD logo [1]
  1. Univ. of California Davis, Sacramento, CA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  2. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  3. Univ. of California Davis, Sacramento, CA (United States); Univ. of London (United Kingdom)
  4. Helmholtz Zentrum München (Germany); Technical Univ. of Munich (Germany)
  5. Oncogenomic Consortium, Mexico City (Mexico)
  6. Wake Forest Univ., Winston-Salem, NC (United States)
  7. Colorado State Univ., Fort Collins, CO (United States)
  8. Univ. of California Davis, Sacramento, CA (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1900155
Report Number(s):
PNNL-SA-174987
Journal ID: ISSN 2079-4991
Grant/Contract Number:  
AC05-76RL01830; AC52-07NA27344
Resource Type:
Accepted Manuscript
Journal Name:
Nanomaterials
Additional Journal Information:
Journal Volume: 12; Journal Issue: 20; Journal ID: ISSN 2079-4991
Publisher:
MDPI
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; radiation; radioprotection; radiomitigation; DNA damage; countermeasure; nanoparticle; human cells; curcumin; nanodisc; ionizing radiation; radiosensitizer

Citation Formats

Evans, Angela C., Martin, Kelly A., Saxena, Manoj, Bicher, Sandra, Wheeler, Elizabeth, Cordova, Emilio J., Porada, Christopher D., Almeida-Porada, Graça, Kato, Takamitsu A., Wilson, Paul F., and Coleman, Matthew A. Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner. United States: N. p., 2022. Web. doi:10.3390/nano12203619.
Evans, Angela C., Martin, Kelly A., Saxena, Manoj, Bicher, Sandra, Wheeler, Elizabeth, Cordova, Emilio J., Porada, Christopher D., Almeida-Porada, Graça, Kato, Takamitsu A., Wilson, Paul F., & Coleman, Matthew A. Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner. United States. https://doi.org/10.3390/nano12203619
Evans, Angela C., Martin, Kelly A., Saxena, Manoj, Bicher, Sandra, Wheeler, Elizabeth, Cordova, Emilio J., Porada, Christopher D., Almeida-Porada, Graça, Kato, Takamitsu A., Wilson, Paul F., and Coleman, Matthew A. Sat . "Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner". United States. https://doi.org/10.3390/nano12203619. https://www.osti.gov/servlets/purl/1900155.
@article{osti_1900155,
title = {Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner},
author = {Evans, Angela C. and Martin, Kelly A. and Saxena, Manoj and Bicher, Sandra and Wheeler, Elizabeth and Cordova, Emilio J. and Porada, Christopher D. and Almeida-Porada, Graça and Kato, Takamitsu A. and Wilson, Paul F. and Coleman, Matthew A.},
abstractNote = {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 137Cs 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.},
doi = {10.3390/nano12203619},
journal = {Nanomaterials},
number = 20,
volume = 12,
place = {United States},
year = {Sat Oct 15 00:00:00 EDT 2022},
month = {Sat Oct 15 00:00:00 EDT 2022}
}

Works referenced in this record:

Effect of curcumin on amyloid‐like aggregates generated from methionine‐oxidized apolipoprotein A‐I
journal, January 2018

  • Krishnamoorthy, Aparna; Tavoosi, Narjes; Chan, Gary K. L.
  • FEBS Open Bio, Vol. 8, Issue 2
  • DOI: 10.1002/2211-5463.12372

Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX‐2, MMP‐9, VEGF and CXCR4 expression in an orthotopic mouse model
journal, July 2009

  • Kunnumakkara, Ajaikumar B.; Diagaradjane, Parmeswaran; Anand, Preetha
  • International Journal of Cancer, Vol. 125, Issue 9
  • DOI: 10.1002/ijc.24593

Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy
journal, January 2019

  • Mortezaee, Keywan; Salehi, Ensieh; Mirtavoos‐mahyari, Hanifeh
  • Journal of Cellular Physiology, Vol. 234, Issue 8
  • DOI: 10.1002/jcp.28122

Curcumin, the golden nutraceutical: multitargeting for multiple chronic diseases: Curcumin: from kitchen to clinic
journal, October 2016

  • Kunnumakkara, Ajaikumar B.; Bordoloi, Devivasha; Padmavathi, Ganesan
  • British Journal of Pharmacology, Vol. 174, Issue 11
  • DOI: 10.1111/bph.13621

Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy
journal, April 2007

  • Bisht, Savita; Feldmann, Georg; Soni, Sheetal
  • Journal of Nanobiotechnology, Vol. 5, Issue 1
  • DOI: 10.1186/1477-3155-5-3

Turmeric: A condiment, cosmetic and cure
journal, January 2018

  • Gopinath, Hima; Karthikeyan, Kaliaperumal
  • Indian Journal of Dermatology, Venereology and Leprology, Vol. 84, Issue 1
  • DOI: 10.4103/ijdvl.IJDVL_1143_16

Curcumin protects against radiation-induced acute and chronic cutaneous toxicity in mice and decreases mRNA expression of inflammatory and fibrogenic cytokines
journal, July 2006

  • Okunieff, Paul; Xu, Jianhua; Hu, Dongping
  • International Journal of Radiation Oncology*Biology*Physics, Vol. 65, Issue 3
  • DOI: 10.1016/j.ijrobp.2006.03.025

Photophysical studies on curcumin-sophorolipid nanostructures: applications in quorum quenching and imaging
journal, February 2018

  • Vasudevan, Sahana; Prabhune, Asmita A.
  • Royal Society Open Science, Vol. 5, Issue 2
  • DOI: 10.1098/rsos.170865

Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer
journal, April 2007


Anticancer effect of curcumin inhibits cell growth through miR-21/PTEN/Akt pathway in breast cancer cell
journal, April 2017

  • Wang, Xinzheng; Hang, Yakai; Liu, Jinbiao
  • Oncology Letters, Vol. 13, Issue 6
  • DOI: 10.3892/ol.2017.6053

Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice
journal, May 2010

  • Lee, James C.; Kinniry, Paul A.; Arguiri, Evguenia
  • Radiation Research, Vol. 173, Issue 5
  • DOI: 10.1667/RR1522.1

53BP1: function and mechanisms of focal recruitment
journal, July 2009

  • FitzGerald, Jennifer E.; Grenon, Muriel; Lowndes, Noel F.
  • Biochemical Society Transactions, Vol. 37, Issue 4
  • DOI: 10.1042/BST0370897

Curcumin suppresses glioblastoma cell proliferation by p-AKT/mTOR pathway and increases the PTEN expression
journal, August 2020


Curcumin for Radiation Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Thirty Breast Cancer Patients
journal, July 2013

  • Ryan, Julie L.; Heckler, Charles E.; Ling, Marilyn
  • Radiation Research, Vol. 180, Issue 1
  • DOI: 10.1667/RR3255.1

Protective effects of chlorogenic acid, curcumin and β-carotene against γ-radiation-induced in vivo chromosomal damage
journal, November 1993


Curcumin: A Review of Its’ Effects on Human Health
journal, October 2017


Protective effect of curcumin on γ-radiation induced DNA damage and lipid peroxidation in cultured human lymphocytes
journal, December 2006

  • Srinivasan, M.; Rajendra Prasad, N.; Menon, Venugopal P.
  • Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol. 611, Issue 1-2
  • DOI: 10.1016/j.mrgentox.2006.07.002

Nanocurcumin restores aberrant miRNA expression profile in multiple sclerosis, randomized, double‐blind, placebo‐controlled trial
journal, January 2018

  • Dolati, Sanam; Aghebati‐Maleki, Leili; Ahmadi, Majid
  • Journal of Cellular Physiology, Vol. 233, Issue 7
  • DOI: 10.1002/jcp.26301

Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform
journal, March 2014


Protection against ionizing radiation by antioxidant nutrients and phytochemicals
journal, July 2003


Recognition, signaling, and repair of DNA double-strand breaks produced by ionizing radiation in mammalian cells: The molecular choreography
journal, October 2012


Cationic HDL mimetics enhance in vivo delivery of self-replicating mRNA
journal, February 2020

  • He, Wei; Evans, Angela C.; Rasley, Amy
  • Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 24
  • DOI: 10.1016/j.nano.2020.102154

Curcumin nanodisks: formulation and characterization
journal, April 2011

  • Ghosh, Mistuni; Singh, Amareshwar T. K.; Xu, Wenwei
  • Nanomedicine: Nanotechnology, Biology and Medicine, Vol. 7, Issue 2
  • DOI: 10.1016/j.nano.2010.08.002

Enhancing the oral bioavailability of curcumin using solid lipid nanoparticles
journal, January 2020


Cell-free production of a functional oligomeric form of a Chlamydia major outer-membrane protein (MOMP) for vaccine development
journal, July 2017

  • He, Wei; Felderman, Martina; Evans, Angela C.
  • Journal of Biological Chemistry, Vol. 292, Issue 36
  • DOI: 10.1074/jbc.M117.784561

Acceleration of wound repair by curcumin in the excision wound of mice exposed to different doses of fractionated γ radiation
journal, August 2011


Improvement in oxidative stress and antioxidant parameters in β-thalassemia/Hb E patients treated with curcuminoids
journal, March 2010


Influence of Piperine on the Pharmacokinetics of Curcumin in Animals and Human Volunteers
journal, May 1998


Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells
journal, April 2008

  • Kunwar, A.; Barik, A.; Mishra, B.
  • Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1780, Issue 4
  • DOI: 10.1016/j.bbagen.2007.11.016

Curcumin suppresses multiple DNA damage response pathways and has potency as a sensitizer to PARP inhibitor
journal, July 2013

  • Ogiwara, Hideaki; Ui, Ayako; Shiotani, Bunsyo
  • Carcinogenesis, Vol. 34, Issue 11
  • DOI: 10.1093/carcin/bgt240

Cell-free expression of functional receptor tyrosine kinases
journal, August 2015

  • He, Wei; Scharadin, Tiffany M.; Saldana, Matthew
  • Scientific Reports, Vol. 5, Issue 1
  • DOI: 10.1038/srep12896

Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay
journal, August 2014

  • Sebastià, N.; Montoro, A.; Hervás, D.
  • Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 766-767
  • DOI: 10.1016/j.mrfmmm.2014.05.006

Curcumin regulates proliferation, autophagy, and apoptosis in gastric cancer cells by affecting PI3K and P53 signaling
journal, January 2018

  • Fu, Hongbing; Wang, Changming; Yang, Dejun
  • Journal of Cellular Physiology, Vol. 233, Issue 6
  • DOI: 10.1002/jcp.26190

Bioavailability of Curcumin: Problems and Promises
journal, November 2007

  • Anand, Preetha; Kunnumakkara, Ajaikumar B.; Newman, Robert A.
  • Molecular Pharmaceutics, Vol. 4, Issue 6
  • DOI: 10.1021/mp700113r

Curcumin-Loaded Solid Lipid Nanoparticles Enhanced Anticancer Efficiency in Breast Cancer
journal, June 2018


ApoE enhances nanodisk-mediated curcumin delivery to glioblastoma multiforme cells
journal, May 2014

  • Ghosh, Mistuni; Ryan, Robert O.
  • Nanomedicine, Vol. 9, Issue 6
  • DOI: 10.2217/nnm.13.35

Downregulation of PI3-K/Akt/PTEN pathway and activation of mitochondrial intrinsic apoptosis by Diclofenac and Curcumin in colon cancer
journal, February 2015

  • Rana, Chandan; Piplani, Honit; Vaish, Vivek
  • Molecular and Cellular Biochemistry, Vol. 402, Issue 1-2
  • DOI: 10.1007/s11010-015-2330-5

Targeting of cancer cell death mechanisms by curcumin: Implications to cancer therapy
journal, September 2021

  • Yu, Chong; Yang, Bo; Najafi, Masoud
  • Basic & Clinical Pharmacology & Toxicology, Vol. 129, Issue 6
  • DOI: 10.1111/bcpt.13648

γ-H2AX as a biomarker of DNA damage induced by ionizing radiation in human peripheral blood lymphocytes and artificial skin
journal, April 2009

  • Redon, Christophe E.; Dickey, Jennifer S.; Bonner, William M.
  • Advances in Space Research, Vol. 43, Issue 8
  • DOI: 10.1016/j.asr.2008.10.011

Dose escalation of a curcuminoid formulation
journal, March 2006

  • Lao, Christopher D.; Ruffin, Mack T.; Normolle, Daniel
  • BMC Complementary and Alternative Medicine, Vol. 6, Issue 1
  • DOI: 10.1186/1472-6882-6-10

Curcumin regulates the miR-21/PTEN/Akt pathway and acts in synergy with PD98059 to induce apoptosis of human gastric cancer MGC-803 cells
journal, February 2019

  • Qiang, Zhanrong; Meng, Lingyu; Yi, Caixia
  • Journal of International Medical Research, Vol. 47, Issue 3
  • DOI: 10.1177/0300060518822213

Inter-individual variation in DNA double-strand break repair in human fibroblasts before and after exposure to low doses of ionizing radiation
journal, January 2010

  • Wilson, Paul F.; Nham, Peter B.; Urbin, Salustra S.
  • Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 683, Issue 1-2, p. 91-97
  • DOI: 10.1016/j.mrfmmm.2009.10.013

Curcumin Modulates miR-19/PTEN/AKT/p53 Axis to Suppress Bisphenol A-induced MCF-7 Breast Cancer Cell Proliferation
journal, May 2014

  • Li, Xiaoting; Xie, Wei; Xie, Chunfeng
  • Phytotherapy Research, Vol. 28, Issue 10
  • DOI: 10.1002/ptr.5167

Curcumin induces permanent growth arrest of human colon cancer cells: Link between senescence and autophagy
journal, June 2012

  • Mosieniak, Grazyna; Adamowicz, Marek; Alster, Olga
  • Mechanisms of Ageing and Development, Vol. 133, Issue 6
  • DOI: 10.1016/j.mad.2012.05.004

Liposomal curcumin and its application in cancer
journal, August 2017

  • Feng, Ting; Wei, Yumeng; Lee, Robert
  • International Journal of Nanomedicine, Vol. Volume 12
  • DOI: 10.2147/IJN.S132434

Curcumin potentiates laryngeal squamous carcinoma radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression
journal, June 2020