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Article

Characterization of Redox-Responsive LXR-Activating Nanoparticle Formulations in Primary Mouse Macrophages

1
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada
2
University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, K1H 8M5, Canada
*
Authors to whom correspondence should be addressed.
These authors have equal contribution.
Academic Editor: Rosaria Rinaldi
Molecules 2019, 24(20), 3751; https://doi.org/10.3390/molecules24203751
Received: 6 August 2019 / Revised: 10 October 2019 / Accepted: 16 October 2019 / Published: 18 October 2019
(This article belongs to the Special Issue Application of Novel Polymeric Nanoparticles in Nanomedicine)
Activation of the transcription factor liver X receptor (LXR) has beneficial effects on macrophage lipid metabolism and inflammation, making it a potential candidate for therapeutic targeting in cardiometabolic disease. While small molecule delivery via nanomedicine has promising applications for a number of chronic diseases, questions remain as to how nanoparticle formulation might be tailored to suit different tissue microenvironments and aid in drug delivery. In the current study, we aimed to compare the in vitro drug delivering capability of three nanoparticle (NP) formulations encapsulating the LXR activator, GW-3965. We observed little difference in the base characteristics of standard PLGA-PEG NP when compared to two redox-active polymeric NP formulations, which we called redox-responsive (RR)1 and RR2. Moreover, we also observed similar uptake of these NP into primary mouse macrophages. We used the transcript and protein expression of the cholesterol efflux protein and LXR target ATP-binding cassette A1 (ABCA1) as a readout of GW-3956-induced LXR activation. Following an initial acute uptake period that was meant to mimic circulating exposure in vivo, we determined that although the induction of transcript expression was similar between NPs, treatment with the redox-sensitive RR1 NPs resulted in a higher level of ABCA1 protein. Our results suggest that NP formulations responsive to cellular cues may be an effective tool for targeted and disease-specific drug release. View Full-Text
Keywords: nanomedicine; nanoparticles; drug delivery; LXR agonists; ABCA1; macrophages; redox-responsive nanoparticle nanomedicine; nanoparticles; drug delivery; LXR agonists; ABCA1; macrophages; redox-responsive nanoparticle
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MDPI and ACS Style

Smith, T.K.T.; Kahiel, Z.; LeBlond, N.D.; Ghorbani, P.; Farah, E.; Al-Awosi, R.; Cote, M.; Gadde, S.; Fullerton, M.D. Characterization of Redox-Responsive LXR-Activating Nanoparticle Formulations in Primary Mouse Macrophages. Molecules 2019, 24, 3751. https://doi.org/10.3390/molecules24203751

AMA Style

Smith TKT, Kahiel Z, LeBlond ND, Ghorbani P, Farah E, Al-Awosi R, Cote M, Gadde S, Fullerton MD. Characterization of Redox-Responsive LXR-Activating Nanoparticle Formulations in Primary Mouse Macrophages. Molecules. 2019; 24(20):3751. https://doi.org/10.3390/molecules24203751

Chicago/Turabian Style

Smith, Tyler K. T., Zaina Kahiel, Nicholas D. LeBlond, Peyman Ghorbani, Eliya Farah, Refel Al-Awosi, Marceline Cote, Suresh Gadde, and Morgan D. Fullerton. 2019. "Characterization of Redox-Responsive LXR-Activating Nanoparticle Formulations in Primary Mouse Macrophages" Molecules 24, no. 20: 3751. https://doi.org/10.3390/molecules24203751

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