RRC ID |
44363
|
著者 |
Wang X, Li X, Ito A, Sogo Y, Ohno T.
|
タイトル |
Particle-size-dependent toxicity and immunogenic activity of mesoporous silica-based adjuvants for tumor immunotherapy.
|
ジャーナル |
Acta Biomater
|
Abstract |
Conventionally used adjuvants alone are insufficient for triggering cell-mediated immunity, although they have been successfully developed to elicit protective antibody responses in some vaccines. Here, with the aim of eliciting cell-mediated immunity, pathogen-associated molecular patterns (PAMPs) were immobilized with apatite within the pores and on the surface of mesoporous silica (MS) with particle sizes from 30 to 200nm to prepare novel MS-Ap-PAMP adjuvants, which showed cell-mediated anti-tumor immunity that was markedly improved compared to commercial alum adjuvant in vitro and in vivo. The toxicity and antitumor immunity of the MS-Ap-PAMP adjuvants were evaluated in vitro and in vivo. MS with a particle size of 200nm showed minimum in vitro cytotoxicity to NIH3T3 cells, particularly at concentrations no higher than 100μgml(-1). In particular, apatite precipitation within the pores and on the surface of MS decreased the in vitro cytotoxicity of MS particles. The MS-Ap-PAMP adjuvants showed the maximum in vitro immunogenic activity among original culture medium, PAMP and alum-PAMP. Moreover, injection of the MS-Ap-PAMP adjuvant in combination with liquid-nitrogen-treated tumor tissue (derived from Lewis lung carcinoma cells) into C57BL/6 mice markedly inhibited in vivo tumor recurrence and the development of rechallenged tumor compared to those with commercial alum adjuvant. The MS-Ap-PAMP adjuvant contributed to the elicitation of a potent systemic antitumor immunity without obvious toxicity in vivo.
|
巻・号 |
9(7)
|
ページ |
7480-9
|
公開日 |
2013-7-1
|
DOI |
10.1016/j.actbio.2013.03.031
|
PII |
S1742-7061(13)00158-X
|
PMID |
23541601
|
MeSH |
Adjuvants, Immunologic / therapeutic use*
Animals
Cancer Vaccines / immunology*
Cancer Vaccines / therapeutic use*
Carcinoma, Lewis Lung / immunology*
Carcinoma, Lewis Lung / therapy*
Cell Line, Tumor
Cell Survival / drug effects
Mice
Mice, Inbred C57BL
NIH 3T3 Cells
Particle Size
Porosity
Silicon Dioxide / immunology*
Silicon Dioxide / therapeutic use*
Treatment Outcome
|
IF |
7.242
|
引用数 |
39
|
WOS 分野
|
ENGINEERING, BIOMEDICAL
MATERIALS SCIENCE, BIOMATERIALS
|
リソース情報 |
ヒト・動物細胞 |
THP-1(RCB1189) |