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Selective topotecan delivery to cancer cells by targeted pH-sensitive mesoporous silica nanoparticles

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Martínez Carmona, Marina y Lozano Borregón, Daniel y Colilla, Montserrat y Vallet Regí, María (2016) Selective topotecan delivery to cancer cells by targeted pH-sensitive mesoporous silica nanoparticles. RSC Advances, 6 (56). pp. 50923-50932. ISSN 2046-2069

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Resumen

Topotecan (TOP), a water-soluble derivative of camptothecin, is a potent antitumor agent that is receiving growing attention for the treatment of several types of cancer. However, one of the major constraints in the clinical use of this drug is its inactivation at the physiological pH of 7.4. Mesoporous silica nanoparticles (MSNs) constitute promising nanocarriers to circumvent this issue. Herein TOP has been encapsulated into MSNs and the nanosystem has been provided with selectivity towards tumor cells, which permits releasing the active form of the molecule at the acidic cell compartments (endo/lysosomes; pH <= 5.5) following nanoparticle internalization. For this purpose, MSNs have been coated with a multifunctional gelatin shell that: (i) protects TOP from hydrolysis and prevents its premature release; (ii) acts as a pH-sensitive layer; and (iii) provides multiple anchoring points for the grafting of targeting ligands, such as folic acid (FA), for selective internalization in tumor cells. In vitro tests demonstrate that cancer cells that overexpress membrane cell surface markers with affinity towards FA, internalize a higher percentage of nanoparticles than healthy cells, which do not overexpress such markers. Moreover, the nanosystems are efficient at killing tumor cells, whereas they do not decrease the viability of normal cells. In contrast, free TOP failed to kill both cell lines, which can be ascribed to the inactivation of the drug. This novel nanodevice constitutes a step forward toward the design of novel weapons to fight against cancer.


Tipo de documento:Artículo
Información Adicional:

RESEARCHER ID M-3378-2014 (María Vallet Regí)
ORCID 0000-0002-6104-4889 (María Vallet Regí)
RESEARCHER ID B-5081-2017 (Daniel Lozano Borregón)
ORCID 0000-0001-5902-9201 (Daniel Lozano Borregón)

Palabras clave:Transmission electron-microscopy; Iron-oxide Nanoparticles; Drug-delivery; Folate receptor; Biomedical applications; Antitumor therapy; Gelatin matrices; Anticancer drug; Release; System
Materias:Ciencias > Química > Materiales
Ciencias > Química > Química inorgánica
Código ID:40837
Depositado:01 Feb 2017 11:48
Última Modificación:21 May 2017 23:01

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