PMID- 29737353
OWN - NLM
STAT- MEDLINE
DCOM- 20190117
LR  - 20240314
IS  - 2040-3372 (Electronic)
IS  - 2040-3364 (Print)
IS  - 2040-3364 (Linking)
VI  - 10
IP  - 19
DP  - 2018 May 17
TI  - Induction of necrotic cell death and activation of STING in the tumor 
      microenvironment via cationic silica nanoparticles leading to enhanced antitumor 
      immunity.
PG  - 9311-9319
LID - 10.1039/c8nr01376d [doi]
AB  - Nanotechnology has demonstrated tremendous clinical utility, with potential 
      applications in cancer immunotherapy. Although nanoparticles with intrinsic 
      cytotoxicity are often considered unsuitable for clinical applications, such 
      toxicity may be harnessed in the fight against cancer. Nanoparticle-associated 
      toxicity can induce acute necrotic cell death, releasing tumor-associated 
      antigens which may be captured by antigen-presenting cells to initiate or amplify 
      tumor immunity. To test this hypothesis, cytotoxic cationic silica nanoparticles 
      (CSiNPs) were directly administered into B16F10 melanoma implanted in C57BL/6 
      mice. CSiNPs caused plasma membrane rupture and oxidative stress of tumor cells, 
      inducing local inflammation, tumor cell death and the release of tumor-associated 
      antigens. The CSiNPs were further complexed with bis-(3'-5')-cyclic dimeric 
      guanosine monophosphate (c-di-GMP), a molecular adjuvant which activates the 
      stimulator of interferon genes (STING) in antigen-presenting cells. Compared with 
      unformulated c-di-GMP, the delivery of c-di-GMP with CSiNPs markedly prolonged 
      its local retention within the tumor microenvironment and activated 
      tumor-infiltrating antigen-presenting cells. The combination of CSiNPs and a 
      STING agonist showed dramatically increased expansion of antigen-specific CD8+ T 
      cells, and potent tumor growth inhibition in murine melanoma. These results 
      demonstrate that cationic nanoparticles can be used as an effective in situ 
      vaccine platform which simultaneously causes tumor destruction and immune 
      activation.
FAU - An, Myunggi
AU  - An M
AD  - Department of Chemical Engineering and Materials Science, Wayne State University, 
      Detroit, Michigan 48202, USA. haipengl.liu@wayne.edu.
FAU - Yu, Chunsong
AU  - Yu C
FAU - Xi, Jingchao
AU  - Xi J
FAU - Reyes, Joyce
AU  - Reyes J
FAU - Mao, Guangzhao
AU  - Mao G
FAU - Wei, Wei-Zen
AU  - Wei WZ
FAU - Liu, Haipeng
AU  - Liu H
LA  - eng
GR  - P30 CA022453/CA/NCI NIH HHS/United States
GR  - R01 CA076340/CA/NCI NIH HHS/United States
PT  - Journal Article
PL  - England
TA  - Nanoscale
JT  - Nanoscale
JID - 101525249
RN  - 0 (Membrane Proteins)
RN  - 0 (Sting1 protein, mouse)
RN  - 61093-23-0 (bis(3',5')-cyclic diguanylic acid)
RN  - 7631-86-9 (Silicon Dioxide)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes
MH  - *Cell Death
MH  - Cyclic GMP/administration & dosage/analogs & derivatives
MH  - Female
MH  - Melanoma, Experimental/*immunology/therapy
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Nanoparticles
MH  - Oxidative Stress
MH  - *Silicon Dioxide
MH  - *Tumor Microenvironment
PMC - PMC5969905
MID - NIHMS966395
COIS- Conflicts of interest There are no conflicts to declare.
EDAT- 2018/05/09 06:00
MHDA- 2019/01/18 06:00
PMCR- 2019/05/17
CRDT- 2018/05/09 06:00
PHST- 2018/05/09 06:00 [pubmed]
PHST- 2019/01/18 06:00 [medline]
PHST- 2018/05/09 06:00 [entrez]
PHST- 2019/05/17 00:00 [pmc-release]
AID - 10.1039/c8nr01376d [doi]
PST - ppublish
SO  - Nanoscale. 2018 May 17;10(19):9311-9319. doi: 10.1039/c8nr01376d.