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

Autor: Smith TKT; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada. tsmit121@uottawa.ca.; University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, K1H 8M5, Canada. tsmit121@uottawa.ca., Kahiel Z; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada. zkahi017@uottawa.ca., LeBlond ND; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada. nlebl062@uottawa.ca.; University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, K1H 8M5, Canada. nlebl062@uottawa.ca., Ghorbani P; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada. pghor093@uottawa.ca.; University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, K1H 8M5, Canada. pghor093@uottawa.ca., Farah E; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada. efara031@uottawa.ca., Al-Awosi R; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada. ralaw053@uottawa.ca., Cote M; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada. marceline.cote@uottawa.ca.; University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, K1H 8M5, Canada. marceline.cote@uottawa.ca., Gadde S; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada. sgadde@uottawa.ca.; University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, K1H 8M5, Canada. sgadde@uottawa.ca., Fullerton MD; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada. morgan.fullerton@uottawa.ca.; University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, K1H 8M5, Canada. morgan.fullerton@uottawa.ca.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2019 Oct 18; Vol. 24 (20). Date of Electronic Publication: 2019 Oct 18.
DOI: 10.3390/molecules24203751
Abstrakt: 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.
Databáze: MEDLINE
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