title: Particle-size-dependent toxicity and immunogenic activity of mesoporous silica-based adjuvants for tumor immunotherapy.
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.
authors.affiliation: Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. xp-wang@aist.go.jp
authors.forename: Xiupeng
authors.initials: X
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ito
authors.forename: Yu
authors.initials: Y
authors.lastname: Sogo
authors.forename: Tadao
authors.initials: T
authors.lastname: Ohno
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000276:immunology* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D012822:Silicon Dioxide