@article {1170231,
	title = {Targeted Nanotherapeutics Encapsulating Liver X Receptor Agonist GW3965 Enhance Antiatherogenic Effects without Adverse Effects on Hepatic Lipid Metabolism in Ldlr Mice},
	journal = {Adv Healthc Mater},
	volume = {6},
	number = {20},
	year = {2017},
	month = {2017 Oct},
	abstract = {The pharmacological manipulation of liver X receptors (LXRs) has been an attractive therapeutic strategy for atherosclerosis treatment as they control reverse cholesterol transport and inflammatory response. This study presents the development and efficacy of nanoparticles (NPs) incorporating the synthetic LXR agonist GW3965 (GW) in targeting atherosclerotic lesions. Collagen IV (Col IV) targeting ligands are employed to functionalize the NPs to improve targeting to the atherosclerotic plaque, and formulation parameters such as the length of the polyethylene glycol (PEG) coating molecules are systematically optimized. In vitro studies indicate that the GW-encapsulated NPs upregulate the LXR target genes and downregulate proinflammatory mediator in macrophages. The Col IV-targeted NPs encapsulating GW (Col IV-GW-NPs) successfully reaches atherosclerotic lesions when administered for 5 weeks to mice with preexisting lesions, substantially reducing macrophage content (≈30\%) compared to the PBS group, which is with greater efficacy versus nontargeting NPs encapsulating GW (GW-NPs) (≈18\%). In addition, mice administered the Col IV-GW-NPs do not demonstrate increased hepatic lipid biosynthesis or hyperlipidemia during the treatment period, unlike mice injected with the free GW. These findings suggest a new form of LXR-based therapeutics capable of enhanced delivery of the LXR agonist to atherosclerotic lesions without altering hepatic lipid metabolism.},
	keywords = {Animals, Atherosclerosis, Benzoates, Benzylamines, Cells, Cultured, Cholesterol, Collagen Type IV, Disease Models, Animal, Drug Carriers, Lipid Metabolism, Liver, Liver X Receptors, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Nanomedicine, Nanoparticles, Polyethylene Glycols, Receptors, LDL, Triglycerides},
	issn = {2192-2659},
	doi = {10.1002/adhm.201700313},
	author = {Yu, Mikyung and Amengual, Jaume and Menon, Arjun and Kamaly, Nazila and Zhou, Felix and Xu, Xiaoding and Saw, Phei Er and Lee, Seung-Joo and Si, Kevin and Ortega, Carleena Angelica and Choi, Won Il and Lee, In-Hyun and Bdour, Yazan and Shi, Jinjun and Mahmoudi, Morteza and Jon, Sangyong and Fisher, Edward A and Farokhzad, Omid C}
}
