RESUMEN
Nanoparticles have been widely used as platforms for biomolecular sensing because of their high specific surface area and attractive properties depending on their constituents and structures. Nevertheless, it remains challenging to develop nanoparticulate sensing platforms that are easily storable without aggregation and conjugatable with various ligands in a simple manner. Herein, we demonstrate that nanoparticulate assemblies of cello-oligosaccharides with terminal azido groups are promising candidates. Azidated cello-oligosaccharides can be readily synthesized via the enzyme-catalyzed oligomerization reaction. This study characterized the assembled structures of azidated cello-oligosaccharides produced during the enzymatic synthesis and revealed that the terminal azidated cello-oligosaccharides formed rectangular nanosheet-shaped lamellar crystals. The azido groups located on the nanosheet surfaces were successfully exploited for antigen conjugation via the click chemistry. The resultant antigen-conjugated nanosheets allowed for the quantitative and specific detection of a corresponding antibody, even in 10% serum, owing to the antifouling properties of cello-oligosaccharide assemblies against proteins. It was found that the functionalized nanosheets were redispersible in water after freeze-drying. This remarkable characteristic is attributed to the well-hydrated saccharide residues on the nanosheet surfaces. Moreover, the antibody detection capability did not decline after the thermal treatment of the functionalized nanosheets in a freeze-dried state. Our findings contribute to developing convenient nanoparticulate biomolecular sensing platforms.
Asunto(s)
Química Clic , Ensayo de Materiales , Nanopartículas , Oligosacáridos , Tamaño de la Partícula , Nanopartículas/química , Oligosacáridos/química , Materiales Biocompatibles/química , Materiales Biocompatibles/síntesis química , Liofilización , Estructura Molecular , Técnicas BiosensiblesRESUMEN
Block copolymer micelles functionalized with tetrazine groups can act as nanoreactors to activate a trans-cyclooctene-functionalized prodrug for releasing anticancer drugs via a bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) reaction. In addition, the IEDDA reaction can be accelerated in the micellar nanoreactor system compared to the free tetrazine system. Moreover, In vivo prodrug activation in a mouse tumor model led to the inhibition of tumor growth without significant systemic toxicity. These results demonstrated their potential for applications as bioorthogonal micellar nanoreactors for cancer chemotherapy.
Asunto(s)
Compuestos Heterocíclicos , Neoplasias , Profármacos , Animales , Reacción de Cicloadición , Electrones , Ratones , Micelas , Nanotecnología , Neoplasias/tratamiento farmacológico , Profármacos/farmacologíaRESUMEN
Transplantable catalytic reactors have attracted considerable attention as therapeutic biomedical materials. However, existing transplantable reactors such as biocatalytic films are limited by their invasiveness. Here, we report the fabrication of biocatalytic supramolecular hydrogels via self-assembly of amphiphilic glycopeptides. We show that the hydrogels have shear-thinning properties, demonstrating their potential to be administered using a syringe. Enzymes can be loaded into the hydrogels by simply adding enzyme solution, and the enzyme-loaded hydrogels can transform a prodrug into an anticancer drug that inhibits tumor cell growth. This study demonstrates the potential of these biocatalytic hydrogels as injectable therapeutic reactors for enzyme prodrug therapy.