RESUMO
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.
Assuntos
Nanopartículas/administração & dosagem , Neoplasias/imunologia , Neoplasias/terapia , Dióxido de Silício/administração & dosagem , Dióxido de Silício/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células/efeitos dos fármacos , Feminino , Imunoglobulinas/imunologia , Memória Imunológica/efeitos dos fármacos , Memória Imunológica/imunologia , Imunoterapia/métodos , Interferon gama/imunologia , Interleucinas/imunologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Baço/efeitos dos fármacos , Baço/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologiaRESUMO
A Th1 immune response is required for modern vaccines as the most commonly used alum adjuvant has weak capacity for inducing Th1 immune response. Herein, rod-shaped hydroxyapatite (HA), magnesium-substituted HA (MgHA) and zinc-substituted HA (ZnHA) nanoparticles with irregular nanopores were synthesized and used as immunoadjuvants. Magnesium and zinc substitution in HA showed no influence on morphology, particle size, zeta potential and surface area of the nanoparticles. The rod-shaped MgHA and ZnHA nanoparticles promoted the cellular uptake of a molecular immunopotentiator, stimulated both type 1 and 2 cytokine secretion in vitro that relate to Th1 and Th2 immunity of bone marrow dentritic cells, respectively. The MgHA and ZnHA nanoparticles may be useful as immunoadjuvants for human.