PMID- 35507131
OWN - NLM
STAT- MEDLINE
DCOM- 20220810
LR  - 20220818
IS  - 2190-3948 (Electronic)
IS  - 2190-393X (Print)
IS  - 2190-393X (Linking)
VI  - 12
IP  - 9
DP  - 2022 Sep
TI  - Three-dimensional (3D) liver cell models - a tool for bridging the gap between 
      animal studies and clinical trials when screening liver accumulation and toxicity 
      of nanobiomaterials.
PG  - 2048-2074
LID - 10.1007/s13346-022-01147-0 [doi]
AB  - Despite the exciting properties and wide-reaching applications of 
      nanobiomaterials (NBMs) in human health and medicine, their translation from 
      bench to bedside is slow, with a predominant issue being liver accumulation and 
      toxicity following systemic administration. In vitro 2D cell-based assays and in 
      vivo testing are the most popular and widely used methods for assessing liver 
      toxicity at pre-clinical stages; however, these fall short in predicting toxicity 
      for NBMs. Focusing on in vitro and in vivo assessment, the accurate prediction of 
      human-specific hepatotoxicity is still a significant challenge to researchers. 
      This review describes the relationship between NBMs and the liver, and the 
      methods for assessing toxicity, focusing on the limitations they bring in the 
      assessment of NBM hepatotoxicity as one of the reasons defining the poor 
      translation for NBMs. We will then present some of the most recent advances 
      towards the development of more biologically relevant in vitro liver methods 
      based on tissue-mimetic 3D cell models and how these could facilitate the 
      translation of NBMs going forward. Finally, we also discuss the low public 
      acceptance and limited uptake of tissue-mimetic 3D models in pre-clinical 
      assessment, despite the demonstrated technical and ethical advantages associated 
      with them. 3D culture models for use as in vitro alternatives to traditional 
      methods and conventional in vivo animal testing for testing liver accumulation 
      and toxicity of nanobiomaterials.
CI  - (c) 2022. The Author(s).
FAU - Tutty, Melissa Anne
AU  - Tutty MA
AUID- ORCID: 0000-0002-6705-2492
AD  - Nanomedicine and Molecular Imaging Group, School of Medicine, Trinity 
      Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin 8, 
      Ireland. tuttym@tcd.ie.
AD  - Laboratory for Biological Characterisation of Advanced Materials (LBCAM), School 
      of Medicine, TTMI, Trinity College Dublin, Dublin 8, Ireland. tuttym@tcd.ie.
FAU - Movia, Dania
AU  - Movia D
AD  - Nanomedicine and Molecular Imaging Group, School of Medicine, Trinity 
      Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin 8, 
      Ireland.
AD  - Laboratory for Biological Characterisation of Advanced Materials (LBCAM), School 
      of Medicine, TTMI, Trinity College Dublin, Dublin 8, Ireland.
AD  - Trinity St James's Cancer Institute, Trinity College Dublin, St James's Hospital, 
      Dublin 8, Ireland.
FAU - Prina-Mello, Adriele
AU  - Prina-Mello A
AUID- ORCID: 0000-0002-4371-2214
AD  - Nanomedicine and Molecular Imaging Group, School of Medicine, Trinity 
      Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin 8, 
      Ireland. prinamea@tcd.ie.
AD  - Laboratory for Biological Characterisation of Advanced Materials (LBCAM), School 
      of Medicine, TTMI, Trinity College Dublin, Dublin 8, Ireland. prinamea@tcd.ie.
AD  - Trinity St James's Cancer Institute, Trinity College Dublin, St James's Hospital, 
      Dublin 8, Ireland. prinamea@tcd.ie.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20220504
PL  - United States
TA  - Drug Deliv Transl Res
JT  - Drug delivery and translational research
JID - 101540061
SB  - IM
MH  - Animals
MH  - *Chemical and Drug Induced Liver Injury
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Hepatocytes
MH  - Humans
MH  - In Vitro Techniques
MH  - Liver
PMC - PMC9066991
OTO - NOTNLM
OT  - 3D models
OT  - Hepatotoxicity
OT  - Liver
OT  - Nanobiomaterials
OT  - Nanomedicine
COIS- The authors declare no competing interests.
EDAT- 2022/05/05 06:00
MHDA- 2022/08/11 06:00
PMCR- 2022/05/04
CRDT- 2022/05/04 11:18
PHST- 2022/03/03 00:00 [accepted]
PHST- 2022/05/05 06:00 [pubmed]
PHST- 2022/08/11 06:00 [medline]
PHST- 2022/05/04 11:18 [entrez]
PHST- 2022/05/04 00:00 [pmc-release]
AID - 10.1007/s13346-022-01147-0 [pii]
AID - 1147 [pii]
AID - 10.1007/s13346-022-01147-0 [doi]
PST - ppublish
SO  - Drug Deliv Transl Res. 2022 Sep;12(9):2048-2074. doi: 10.1007/s13346-022-01147-0. 
      Epub 2022 May 4.