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Cathepsin‐B Induced Controlled Release from Peptide‐Capped Mesoporous Silica Nanoparticles
Authors:Cristina de la Torre  Laura Mondragón  Carmen Coll  Félix Sancenón  María D Marcos  Ramón Martínez‐Máñez  Pedro Amorós  Mar Orzáez
Affiliation:1. Centro de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Unidad Mixta Universidad Politécnica de Valencia‐, Universidad de Valencia (Spain);2. Departamento de Química, Universidad Politécnica de Valencia. Camino de Vera s/n, 46022, Valenicia (Spain);3. CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER‐BBN) (Spain);4. Centre Méditerranéen de Médecine Moléculaire (C3?M), équipe “contr?le métabolique des morts cellulaires” Institut national de la santé et de la recherche médicale (Inserm), U1065, BP 2 3194, 06204, Nice (France);5. Institut de Ciència dels Materials (ICMUV), Universitat de València, P.O. Box 2085, 46071 Valencia (Spain);6. Laboratorio Péptidos y Proteínas. Centro de Investigación Príncipe Felipe., C/Eduardo Primo Yúfera, 3 (junto Oceanogràfic), 46012 Valencia (Spain), Fax: (+34)?96‐328‐97‐01
Abstract:New capped silica mesoporous nanoparticles for intracellular controlled cargo release within cathepsin B expressing cells are described. Nanometric mesoporous MCM‐41 supports loaded with safranin O ( S1‐P ) or doxorubicin ( S2‐P ) containing a molecular gate based on a cathepsin B target peptidic sequence were synthesized. Solids were designed to show “zero delivery” and to display cargo release in the presence of cathepsin B enzyme, which selectively hydrolyzed in vitro the capping peptide sequence. Controlled delivery in HeLa, MEFs WT, and MEFs lacking cathepsin B cell lines were also tested. Release of safranin O and doxorubicin in these cells took place when cathepsin B was active or present. Cells treated with S2‐P showed a fall in cell viability due to nanoparticles internalization, cathepsin B hydrolysis of the capping peptide, and cytotoxic agent delivery, proving the possible use of these nanodevices as new therapeutic tools for cancer treatment.
Keywords:Cathepsin   B  controlled release  gated mesoporous materials  nanoparticles  peptides
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