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Chemistry ; 20(18): 5271-81, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24700694

RESUMO

The synthesis and characterization of two new capped silica mesoporous nanoparticles for controlled delivery purposes are described. Capped hybrid systems consist of MCM-41 nanoparticles functionalized on the outer surface with polymer ε-poly-L-lysine by two different anchoring strategies. In both cases, nanoparticles were loaded with model dye molecule [Ru(bipy)3](2+). An anchoring strategy involved the random formation of urea bonds by the treatment of propyl isocyanate-functionalized MCM-41 nanoparticles with the lysine amino groups located on the ε-poly-L-lysine backbone (solid Ru-rLys-S1). The second strategy involved a specific attachment through the carboxyl terminus of the polypeptide with azidopropyl-functionalized MCM-41 nanoparticles (solid Ru-tLys-S1). Once synthesized, both nanoparticles showed a nearly zero cargo release in water due to the coverage of the nanoparticle surface by polymer ε-poly-L-lysine. In contrast, a remarkable payload delivery was observed in the presence of proteases due to the hydrolysis of the polymer's amide bonds. Once chemically characterized, studies of the viability and the lysosomal enzyme-controlled release of the dye in intracellular media were carried out. Finally, the possibility of using these materials as drug-delivery systems was tested by preparing the corresponding ε-poly-L-lysine capped mesoporous silica nanoparticles loaded with cytotoxic drug camptothecin (CPT), CPT-rLys-S1 and CPT-tLys-S1. Cellular uptake and cell-death induction were studied. The efficiency of both nanoparticles as new potential platforms for cancer treatment was demonstrated.


Assuntos
Preparações de Ação Retardada/química , Nanopartículas/química , Polilisina/química , Dióxido de Silício/química , Linhagem Celular Tumoral , Corantes/administração & dosagem , Preparações de Ação Retardada/metabolismo , Células HeLa , Humanos , Lisossomos/enzimologia , Nanopartículas/metabolismo , Nanopartículas/ultraestrutura , Polilisina/metabolismo , Porosidade , Rutênio/administração & dosagem , Dióxido de Silício/metabolismo
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