PMID- 24261790
OWN - NLM
STAT- MEDLINE
DCOM- 20140826
LR  - 20231104
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Print)
IS  - 1936-0851 (Linking)
VI  - 7
IP  - 12
DP  - 2013 Dec 23
TI  - Engineering an effective immune adjuvant by designed control of shape and 
      crystallinity of aluminum oxyhydroxide nanoparticles.
PG  - 10834-49
LID - 10.1021/nn404211j [doi]
AB  - Adjuvants based on aluminum salts (Alum) are commonly used in vaccines to boost 
      the immune response against infectious agents. However, the detailed mechanism of 
      how Alum enhances adaptive immunity and exerts its adjuvant immune effect remains 
      unclear. Other than being comprised of micrometer-sized aggregates that include 
      nanoscale particulates, Alum lacks specific physicochemical properties to explain 
      activation of the innate immune system, including the mechanism by which 
      aluminum-based adjuvants engage the NLRP3 inflammasome and IL-1beta production. This 
      is putatively one of the major mechanisms required for an adjuvant effect. 
      Because we know that long aspect ratio nanomaterials trigger the NLRP3 
      inflammasome, we synthesized a library of aluminum oxyhydroxide (AlOOH) nanorods 
      to determine whether control of the material shape and crystalline properties 
      could be used to quantitatively assess NLRP3 inflammasome activation and linkage 
      of the cellular response to the material's adjuvant activities in vivo. Using 
      comparison to commercial Alum, we demonstrate that the crystallinity and surface 
      hydroxyl group display of AlOOH nanoparticles quantitatively impact the 
      activation of the NLRP3 inflammasome in human THP-1 myeloid cells or murine bone 
      marrow-derived dendritic cells (BMDCs). Moreover, these in vitro effects were 
      correlated with the immunopotentiation capabilities of the AlOOH nanorods in a 
      murine OVA immunization model. These results demonstrate that shape, 
      crystallinity, and hydroxyl content play an important role in NLRP3 inflammasome 
      activation and are therefore useful for quantitative boosting of antigen-specific 
      immune responses. These results show that the engineered design of aluminum-based 
      adjuvants in combination with dendritic cell property-activity analysis can be 
      used to design more potent aluminum-based adjuvants.
FAU - Sun, Bingbing
AU  - Sun B
AD  - Division of NanoMedicine, Department of Medicine, double daggerCalifornia NanoSystems 
      Institute, and  section signDepartment of Chemistry, University of California , Los Angeles, 
      California 90095, United States.
FAU - Ji, Zhaoxia
AU  - Ji Z
FAU - Liao, Yu-Pei
AU  - Liao YP
FAU - Wang, Meiying
AU  - Wang M
FAU - Wang, Xiang
AU  - Wang X
FAU - Dong, Juyao
AU  - Dong J
FAU - Chang, Chong Hyun
AU  - Chang CH
FAU - Li, Ruibin
AU  - Li R
FAU - Zhang, Haiyuan
AU  - Zhang H
FAU - Nel, Andre E
AU  - Nel AE
FAU - Xia, Tian
AU  - Xia T
LA  - eng
GR  - S10 RR023057/RR/NCRR NIH HHS/United States
GR  - U19 ES019528/ES/NIEHS NIH HHS/United States
GR  - 1S10RR23057/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20131202
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Interleukin-1beta)
RN  - 5QB0T2IUN0 (Aluminum Hydroxide)
RN  - 9006-59-1 (Ovalbumin)
RN  - CPD4NFA903 (Aluminum)
SB  - IM
MH  - Adjuvants, Immunologic/*chemistry
MH  - Aluminum/chemistry
MH  - Aluminum Hydroxide/*chemistry
MH  - Animals
MH  - Cell Line
MH  - Dendritic Cells/cytology
MH  - Female
MH  - Humans
MH  - Immunity, Humoral
MH  - Immunity, Innate
MH  - Inflammation
MH  - Interleukin-1beta/metabolism
MH  - Lysosomes/chemistry
MH  - Metal Nanoparticles/*chemistry
MH  - Mice
MH  - Nanotechnology
MH  - Nanotubes/chemistry
MH  - Ovalbumin/chemistry
MH  - Oxidative Stress
MH  - Surface Properties
PMC - PMC3899397
MID - NIHMS545887
EDAT- 2013/11/23 06:00
MHDA- 2014/08/27 06:00
PMCR- 2014/12/23
CRDT- 2013/11/23 06:00
PHST- 2013/11/23 06:00 [entrez]
PHST- 2013/11/23 06:00 [pubmed]
PHST- 2014/08/27 06:00 [medline]
PHST- 2014/12/23 00:00 [pmc-release]
AID - 10.1021/nn404211j [doi]
PST - ppublish
SO  - ACS Nano. 2013 Dec 23;7(12):10834-49. doi: 10.1021/nn404211j. Epub 2013 Dec 2.