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)