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Biomaterials ; 34(20): 4860-71, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23562047

RESUMO

The ability of some malignant cells to evade immunosurveillance has been a major contribution to the inability of the host's immune system to eradicate the neoplastic cells. This has led to the development of various immunological strategies to augment the host immune response as part of cancer treatment. In this study, we developed folic acid (FA)/secondary lymphoid tissue chemokine (CCL21)/upconversion fluorescent nanoparticles (UCNs) conjugates as a targeting and delivery system to attract immune cells to folate receptor (FR) expressing tumor cells. Our data show that FA-conjugated UCNs@mesoporous silica specifically target FR expressing ovarian carcinoma cell line, OVCAR-3, compared to the unconjugated mesoporous silica coated UCNs. Furthermore, the FA-UCNs@mesoporous silica can efficiently cross the endothelial cell monolayer and accumulate in the clusters of OVCAR-3 cells in our endothelial-tumor cell bilayer model. Our migration assay data suggest that the CCL21 loaded into the mesoporous layer is biologically active and can efficiently induce T cells migration in-vitro. No significant cytotoxic effect was observed throughout the study indicating good biocompatibility of the nanoconjugates. As proof-of-concept, we have shown that it is feasible to load biologically active chemokines onto UCNs to modulate T cell migration.


Assuntos
Quimiocina CCL21/farmacologia , Sistemas de Liberação de Medicamentos , Células Endoteliais/metabolismo , Receptor 1 de Folato/metabolismo , Ácido Fólico/farmacologia , Nanopartículas/química , Neoplasias/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Feminino , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Modelos Biológicos , Nanopartículas/ultraestrutura , Neoplasias/patologia , Porosidade , Dióxido de Silício/síntese química , Dióxido de Silício/química , Espectrometria de Fluorescência
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