@article{d0a7464fa91d4e1594085f55bd0d1f7b,
title = "Nanoparticle Drug Delivery Can Reduce the Hepatotoxicity of Therapeutic Cargo",
abstract = "Hepatotoxicity is a key concern in the clinical translation of nanotherapeutics because preclinical studies have consistently shown that nanotherapeutics accumulates extensively in the liver. However, clinical-stage nanotherapeutics have not shown increased hepatotoxicity. Factors that can contribute to the hepatotoxicity of nanotherapeutics beyond the intrinsic hepatotoxicity of nanoparticles (NPs) are poorly understood. Because of this knowledge gap, clinical translation efforts have avoided hepatotoxic molecules. By examining the hepatotoxicity of nanoformulations of known hepatotoxic compounds, it is demonstrated that nanotherapeutics are associated with lower hepatotoxicity than their small-molecule counterparts. It is also found that the reduced hepatotoxicity is related to the uptake of nanotherapeutics by macrophages in the liver. These findings can facilitate further development and clinical translation of nanotherapeutics.",
keywords = "clinical translation, hepatotoxicity, macrophage uptake, nanomedicine, nanotoxicity",
author = "Feifei Yang and Yusra Medik and Liantao Li and Xi Tian and Dong Fu and Brouwer, {Kim L.R.} and Kyle Wagner and Bo Sun and Hossein Sendi and Yu Mi and Wang, {Andrew Z.}",
note = "Funding Information: The authors would like to thank Stephanie Montgomery, Dawud Hilliard, and Ling Wang from Animal Histopathology & Lab Medicine Core for their assistance in hepatotoxicity analysis and histology studies. The authors would like to thank Victoria J. Madden and Kristen K. White from Microscopy Services Laboratory (MSL) for their assistance in TEM and IHC photographing. The authors would like to thank Alain Valdivia, Mark Ross, and Charlene Santos for their assistance in mice tail vein injection. This work was supported by funding from the National Institutes of Health/National Cancer Institute R01GM130590, U54CA198999, R01 CA178748, R01 EB25651‐01A1, UNC Research Opportunity Initiative UNC/State of North Carolina, and Department of Defense Congressionally Directed Medical Research Programs‐Peer Reviewed Cancer Research Program Idea Award CA150391 (A.Z.W.). D.F. and K.L.R.B. were supported by NIH R35 GM122576. F.Y. was supported by funding from CAMS Initiative for Innovative Medicine (CAMS‐I2M 2017‐I2M‐1‐013) and CSC scholarship for studying in the University of North Carolina at Chapel Hill. Funding Information: The authors would like to thank Stephanie Montgomery, Dawud Hilliard, and Ling Wang from Animal Histopathology & Lab Medicine Core for their assistance in hepatotoxicity analysis and histology studies. The authors would like to thank Victoria J. Madden and Kristen K. White from Microscopy Services Laboratory (MSL) for their assistance in TEM and IHC photographing. The authors would like to thank Alain Valdivia, Mark Ross, and Charlene Santos for their assistance in mice tail vein injection. This work was supported by funding from the National Institutes of Health/National Cancer Institute R01GM130590, U54CA198999, R01 CA178748, R01 EB25651-01A1, UNC Research Opportunity Initiative UNC/State of North Carolina, and Department of Defense Congressionally Directed Medical Research Programs-Peer Reviewed Cancer Research Program Idea Award CA150391 (A.Z.W.). D.F. and K.L.R.B. were supported by NIH R35 GM122576. F.Y. was supported by funding from CAMS Initiative for Innovative Medicine (CAMS-I2M 2017-I2M-1-013) and CSC scholarship for studying in the University of North Carolina at Chapel Hill. Publisher Copyright: {\textcopyright} 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2020",
month = feb,
day = "1",
doi = "10.1002/smll.201906360",
language = "English (US)",
volume = "16",
journal = "Small",
issn = "1613-6810",
publisher = "Wiley-VCH Verlag",
number = "7",
}