PMID- 26485167
OWN - NLM
STAT- MEDLINE
DCOM- 20160915
LR  - 20220310
IS  - 1878-7568 (Electronic)
IS  - 1742-7061 (Linking)
VI  - 29
DP  - 2016 Jan
TI  - Submicron-sized hydrogels incorporating cyclic dinucleotides for selective 
      delivery and elevated cytokine release in macrophages.
PG  - 271-281
LID - S1742-7061(15)30155-0 [pii]
LID - 10.1016/j.actbio.2015.10.025 [doi]
AB  - Despite the emerging evidences supporting the potential of cyclic guanosine 
      monophosphate-adenosine monophosphate (cGAMP) as a vaccine adjuvant, few properly 
      designed micro-/nanocarriers for the delivery of cyclic dinucleotides have been 
      developed. In this study, we formulated cGAMP within linear polyethyleneimine 
      (LPEI)/hyaluronic acid (HA) hydrogels via inverse water-in-oil (W/O) 
      emulsion/crosslinking. Spherical and cationic LPEI/HA hydrogels (LH gels) with a 
      size of 455.3+/-3.1nm and a surface charge of 48.7+/-3.7mV were selectively and 
      efficiently delivered into phagocytic macrophage cells, which are one type of 
      antigen-presenting cells (APCs), but not into non-phagocytic fibroblast cells. LH 
      gels incorporating cGAMP (LH/cGAMP gels) elicited excellent induction of the 
      cytokines interferon-beta (IFN-beta) and interleukin-6 (IL-6). In particular, the 
      amount of IFN-beta released by LH hydrogels was significantly increased by 2.5-fold 
      compared to that released by conventional cationic liposomes, such as 
      Lipofectamine. In addition, fabricated LH gels showed superior biocompatibility 
      in phagocytic cell lines and primary bone marrow-derived macrophages (BMDMs). 
      After intramuscular injection with ovalbumin into C57BL/6 mice, LH/cGAMP gels 
      exhibited significantly elevated levels of anti-ovalbumin total IgG in serum and 
      IFN-beta mRNA in spleens. Thus, the newly designed cGAMP-incorporating hydrogels can 
      serve as safe and potent adjuvants for vaccination and immunotherapy. STATEMENT 
      OF SIGNIFICANCE: Since cyclic guanosine monophosphate-adenosine monophosphate 
      (cGAMP) was first found as a second messenger of immune signaling in human 
      systems in February 2013 (Science, 15, 826), several scientific studies have been 
      reported related to the potential of cGAMP as a vaccine adjuvant or additive for 
      immunotherapy. However, only naked cGAMP without carriers were studied via 
      intramuscular or intranasal administration so far. In our study, we first 
      investigated the feasibility of polymeric hydrogels incorporating cGAMP in terms 
      of selective uptake into phagocytic antigen presenting cells (APCs), induction of 
      cytokines, production of target antibodies, and biocompatibility for vaccination 
      and immunotherapy in vitro and in vivo. Therefore, we believe this manuscript 
      would be of great interest to the biomaterial communities especially who are 
      studying immunotherapy.
CI  - Copyright (c) 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights 
      reserved.
FAU - Lee, Eunjoo
AU  - Lee E
AD  - Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, 
      Republic of Korea.
FAU - Jang, Hyo-Eun
AU  - Jang HE
AD  - Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, 
      Republic of Korea.
FAU - Kang, Yoon Young
AU  - Kang YY
AD  - Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, 
      Republic of Korea.
FAU - Kim, Jihyun
AU  - Kim J
AD  - Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, 
      Republic of Korea.
FAU - Ahn, Joong-Hoon
AU  - Ahn JH
AD  - Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, 
      Republic of Korea.
FAU - Mok, Hyejung
AU  - Mok H
AD  - Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, 
      Republic of Korea. Electronic address: hjmok@konkuk.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151017
PL  - England
TA  - Acta Biomater
JT  - Acta biomaterialia
JID - 101233144
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Hydrogels)
RN  - 0 (Interleukin-6)
RN  - 0 (Nucleotides, Cyclic)
RN  - 0 (cyclic guanosine monophosphate-adenosine monophosphate)
RN  - 77238-31-4 (Interferon-beta)
RN  - 9002-98-6 (Polyethyleneimine)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Adjuvants, Immunologic/chemistry/pharmacology
MH  - Animals
MH  - Cell Line
MH  - *Drug Delivery Systems
MH  - Humans
MH  - *Hyaluronic Acid/chemistry/pharmacology
MH  - *Hydrogels/chemistry/pharmacology
MH  - Interferon-beta/*metabolism
MH  - Interleukin-6/*metabolism
MH  - Macrophages/cytology/*metabolism
MH  - Mice
MH  - *Nucleotides, Cyclic/chemistry/pharmacology
MH  - *Polyethyleneimine/chemistry/pharmacology
OTO - NOTNLM
OT  - Adjuvant
OT  - Antigen-presenting cells
OT  - Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP)
OT  - Cytokine
OT  - Hydrogel
OT  - Linear polyethyleneimine (LPEI)
EDAT- 2015/10/21 06:00
MHDA- 2016/09/16 06:00
CRDT- 2015/10/21 06:00
PHST- 2015/05/18 00:00 [received]
PHST- 2015/09/25 00:00 [revised]
PHST- 2015/10/16 00:00 [accepted]
PHST- 2015/10/21 06:00 [entrez]
PHST- 2015/10/21 06:00 [pubmed]
PHST- 2016/09/16 06:00 [medline]
AID - S1742-7061(15)30155-0 [pii]
AID - 10.1016/j.actbio.2015.10.025 [doi]
PST - ppublish
SO  - Acta Biomater. 2016 Jan;29:271-281. doi: 10.1016/j.actbio.2015.10.025. Epub 2015 
      Oct 17.