@article{0ec6b7467af4446da02a0e732643f9df,
title = "Nitric Oxide-Delivering High-Density Lipoprotein-like Nanoparticles as a Biomimetic Nanotherapy for Vascular Diseases",
abstract = "Disorders of blood vessels cause a range of severe health problems. As a powerful vasodilator and cellular second messenger, nitric oxide (NO) is known to have beneficial vascular functions. However, NO typically has a short half-life and is not specifically targeted. On the other hand, high-density lipoproteins (HDLs) are targeted natural nanoparticles (NPs) that transport cholesterol in the systemic circulation and whose protective effects in vascular homeostasis overlap with those of NO. Evolving the AuNP-templated HDL-like nanoparticles (HDL NPs), a platform of bioinspired HDL, we set up a targeted biomimetic nanotherapy for vascular disease that combines the functions of NO and HDL. A synthetic S-nitrosylated (SNO) phospholipid (1,2-dipalmitoyl-sn-glycero-3-phosphonitrosothioethanol) was synthesized and assembled with S-containing phospholipids and the principal protein of HDL, apolipoprotein A-I, to construct NO-delivering HDL-like particles (SNO HDL NPs). SNO HDL NPs self-assemble under mild conditions similar to natural processes, avoiding the complex postassembly modification needed for most synthetic NO-release nanoparticles. In vitro data demonstrate that the SNO HDL NPs merge the functional properties of NO and HDL into a targeted nanocarrier. Also, SNO HDL NPs were demonstrated to reduce ischemia/reperfusion injury in vivo in a mouse kidney transplant model and atherosclerotic plaque burden in a mouse model of atherosclerosis. Thus, the synthesis of SNO HDL NPs provides not only a bioinspired nanotherapy for vascular disease but also a foundation to construct diversified multifunctional platforms based on HDL NPs in the future.",
keywords = "S-nitrosylation, biomimetic, high-density lipoprotein-like nanoparticles, nanotherapy, nitric oxide-delivering, vascular disease",
author = "Rink, {Jonathan S.} and Wangqiang Sun and Sol Misener and Wang, {Jiao Jing} and Zhang, {Zheng Jenny} and Kibbe, {Melina R.} and Dravid, {Vinayak P.} and Subbu Venkatraman and Thaxton, {C. Shad}",
note = "Funding Information: The authors thank Dr. Chiara Musumeci, from the Northwestern University Atomic and Nanoscale Characterization and Experimental Center Scanned Probe Imaging and Development (NUANCE SPID) facility at Northwestern University, for technical assistance and Dr. Nick D. Tsihlis, from the Department of Surgery at the University of North Carolina at Chapel Hill, for his comments and proofreading of the manuscript. For financial support, we thank the NTU-NU Institute for Nanomedicine and NIH/NHLBI BRP 5R01HL116577, NIH/NHLBI T32HL094293, and NIH R01CA167041. The authors would also like to thank the CRN Regenerative Nanomedicine Catalyst Award Program at the Northwestern University and the Simpson Querrey Institute for BioNanotechnology for supporting this research. This work made use of the Keck-II facility of the NUANCE Center at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF NNCI-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. Mass Spectrometry was performed in the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office the U.S. Army Medical Research and Material Command, and Northwestern University provided funding to develop this facility, and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF NNCI-1542205). Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. Funding Information: The authors thank Dr. Chiara Musumeci, from the Northwestern University Atomic and Nanoscale Characterization and Experimental Center Scanned Probe Imaging and Development (NUANCE SPID) facility at Northwestern University, for technical assistance and Dr. Nick D. Tsihlis, from the Department of Surgery at the University of North Carolina at Chapel Hill, for his comments and proofreading of the manuscript. For financial support, we thank the NTU-NU Institute for Nanomedicine and NIH/NHLBI BRP 5R01HL116577, NIH/NHLBI T32HL094293, and NIH R01CA167041. The authors would also like to thank the CRN Regenerative Nanomedicine Catalyst Award Program at the Northwestern University and the Simpson Querrey Institute for BioNanotechnology for supporting this research. This work made use of the Keck-II facility of the NUANCE Center at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF NNCI-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. Mass Spectrometry was performed in the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Material Command, and Northwestern University provided funding to develop this facility, and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF NNCI-1542205). Imaging work was performed at the North-western University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",
year = "2018",
month = feb,
day = "28",
doi = "10.1021/acsami.7b18525",
language = "English (US)",
volume = "10",
pages = "6904--6916",
journal = "ACS applied materials & interfaces",
issn = "1944-8244",
publisher = "American Chemical Society",
number = "8",
}