RESUMO
Appropriate adjuvant aiding in generating robust anticancer immunity is crucial for cancer immunotherapy. Herein, hollow ZnO (HZnO) nanospheres are synthesized by a facile method using carbon nanospheres as the template. The HZnO nanospheres significantly promote the cellular uptake of a model antigen, and cytokine secretion by antigen-presenting cells in vitro. HZnO loaded with ovalbumin and polyinosinic-polycytidylic acid (poly(I:C)) inhibits cancer growth and metastasis to inguinal lymph node in a cancer cell challenge model. Moreover, HZnO loaded with autologous cancer antigens inhibits cancer cell growth in a cancer cell re-challenge model. HZnO nanospheres significantly improve the CD4+ and/or CD8+ T cell population in splenocytes of mice in both cancer cell challenge model and re-challenge model. The HZnO nanospheres can be used for cancer immunotherapy as adjuvant.
Assuntos
Antineoplásicos/farmacologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunidade , Nanosferas/química , Óxido de Zinco/química , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Feminino , Imunidade/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Nanosferas/ultraestrutura , Poli I-C/farmacologiaRESUMO
Hollow and non-hollow mesoporous silica nanospheres are synthesized and used for cancer vaccine adjuvants. The hollow structure of mesoporous silica nanospheres significantly promote cellular uptake of a model cancer antigen by macrophage-like cells in vitro, improve anti-cancer immunity, CD4(+) and CD8(+) T cell populations in splenocytes of mice in vivo.
Assuntos
Adjuvantes Imunológicos/química , Nanosferas/química , Dióxido de Silício/química , Adjuvantes Imunológicos/efeitos adversos , Animais , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/química , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Microscopia Eletroquímica de Varredura , Microscopia Eletrônica de Transmissão , Células NIH 3T3 , Nanosferas/efeitos adversos , Nanosferas/ultraestrutura , PorosidadeRESUMO
A plain mesoporous silica nanoparticle without any immunomodulatory molecules significantly enhances anticancer immunity in vivo. Comprehensive mechanism of mesoporous-silica-nanoparticle-induced cancer immunotherapy is analyzed in this paper. The mesoporous silica nanoparticle promotes both Th1 and Th2 immune responses, as it accelerates lymphocytes proliferation, stimulates IFN-γ, IL-2, IL-4, and IL-10 cytokine secretion by lymphocytes ex vivo, and increases IgG, IgG1, IgG2a, IgM, and IgA antibody titers in mice serum compared with those of alum and adjuvant-free groups. Moreover, the mesoporous silica nanoparticle enhances effector memory CD4(+) and CD8(+) T cell populations in three most important immune organs (bone marrow, lymph node, and spleen) of mice compared with those of alum and adjuvant-free groups three months after adjuvant injection. The present study paves the way for the application of mesoporous silica nanoparticle as immunoadjuvant for cancer immunotherapy.