title: Carbon nanotube-protein carriers enhance size-dependent self-adjuvant antibody response to haptens.
abstract: Carbon nanotubes (CNTs) are nanomaterials with interesting emerging applications. Their properties make CNTs excellent candidates for use as new nanovehicles in drug delivery, immunization and diagnostics. In the current study, we assessed the immune-response-amplifying properties of CNTs to haptens by using azoxystrobin, the first developed strobilurin fungicide, as a model analyte. An azoxystrobin derivative bearing a carboxylated spacer arm (hapten AZc6) was covalently coupled to bovine serum albumin (BSA), and the resulting BSA-AZc6 conjugate was covalently linked to four functionalized CNTs of different shapes and sizes, varying in diameter and length. These four types of CNT-based constructs were obtained using efficient, fast, and easy functionalization procedures based on microwave-assisted chemistry. New Zealand rabbits and BALB/c mice were immunized with BSA-AZc6 alone and with the four CNT-BSA-AZc6 constructs, both with and without Freund's adjuvant. The IgG-type antibody responses were assessed in terms of the titer and affinity, paying special attention to the relationship between the immune response and the size and shape of the employed CNTs. Immunization with CNT-BSA-AZc6 resulted in enhanced titers and excellent affinities for azoxystrobin. More important, remarkable IgG responses were obtained even in the absence of an adjuvant, thus proving the self-adjuvanting capability of CNTs. Immunogens were able to produce strong anti-azoxystrobin immune responses in rabbits even when administered at a BSA-AZc6 conjugate dose as low as 0.05 μg. The short and thick CNT-BSA-AZc6 construct produced the best antibody response under all tested conditions.
authors.affiliation: Department of Biotechnology, Institute of Agrochemistry and Food Technology-IATA, Spanish National Research Council-CSIC, Agustí Escardino 7, 46980 Paterna, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Parra
authors.forename: Antonio
authors.initials: A
authors.lastname: Abad-Somovilla
authors.forename: Josep V
authors.initials: JV
authors.lastname: Mercader
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Taton
authors.forename: Antonio
authors.initials: A
authors.lastname: Abad-Fuentes
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D005659:Fungicides, Industrial / Q000276:immunology; D006241:Haptens / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D008689:Methacrylates; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D011743:Pyrimidines / Q000276:immunology; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D000073739:Strobilurins
chemical_list: D004337:Drug Carriers; D005659:Fungicides, Industrial; D006241:Haptens; D007074:Immunoglobulin G; D008689:Methacrylates; D037742:Nanotubes, Carbon; D011743:Pyrimidines; D000073739:Strobilurins; D012710:Serum Albumin, Bovine; D005620:Freund's Adjuvant; C087670:azoxystrobin
keywords: Antibodies; Antigen delivery; Azoxystrobin; Biomaterials; Carbon nanotubes; Immunization