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Enzyme‐Responsive Intracellular‐Controlled Release Using Silica Mesoporous Nanoparticles Capped with ε‐Poly‐ L ‐lysine
Author(s) -
Mondragón Laura,
Mas Núria,
Ferragud Vicente,
de la Torre Cristina,
Agostini Alessandro,
MartínezMáñez Ramón,
Sancenón Félix,
Amorós Pedro,
PérezPayá Enrique,
Orzáez Mar
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201400148
Subject(s) - mesoporous silica , nanoparticle , lysine , drug delivery , polymer , linker , controlled release , chemistry , surface modification , mesoporous material , polymer chemistry , materials science , combinatorial chemistry , nanotechnology , organic chemistry , amino acid , biochemistry , catalysis , computer science , operating system
Abstract 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.