Enzyme-responsive intracellular-controlled release using silica mesoporous nanoparticles capped with ε-poly-L-lysine.
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.
Centro de Reconocimiento Molecular y Desarrollo Tecnológico, Unidad Mixta Universidad Politécnica de Valencia-Universidad de Valencia, Camino de Vera s/n, 46022 Valencia (Spain); Departamento de Química, Universidad Politécnica de Valencia, Camino de Vera s/n, 46022 Valencia (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBERBBN), Camino de Vera s/n, 46022 Valencia (Spain).
Laura
L
Mondragón
Núria
N
Mas
Vicente
V
Ferragud
Cristina
C
de la Torre
Alessandro
A
Agostini
Ramón
R
Martínez-Máñez
Félix
F
Sancenón
Pedro
P
Amorós
Enrique
E
Pérez-Payá
Mar
M
Orzáez
D045744:Cell Line, Tumor; D004396:Coloring Agents / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011107:Polylysine / Q000737:chemistry* / Q000378:metabolism; D016062:Porosity; D012428:Ruthenium / Q000008:administration & dosage; D012822:Silicon Dioxide / Q000737:chemistry* / Q000378:metabolism
D004396:Coloring Agents; D003692:Delayed-Action Preparations; C509968:MCM-41; D011107:Polylysine; D012822:Silicon Dioxide; D012428:Ruthenium
anchoring strategy; intracellular release; mesoporous materials; nanoparticles; poly-L-lysine