Person: Colilla Nieto, Montserrat
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First Name
Montserrat
Last Name
Colilla Nieto
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
Química Inorgánica
Identifiers
7 results
Search Results
Now showing 1 - 7 of 7
Item Lectin-Conjugated pH-Responsive Mesoporous Silica Nanoparticles for Targeted Bone Cancer Treatment.(Acta Biomaterialia, 2017) Martínez Carmona, Marina; Lozano Borregón, Daniel; Colilla Nieto, Montserrat; Vallet Regí, María Dulce NombreA novel multifunctional nanodevice based in doxorubicin (DOX)-loaded mesoporous silica nanoparticles (MSNs) as nanoplatforms for the assembly of different building blocks has been developed for bone cancer treatment. These building blocks consists of: i) a polyacrylic acid (PAA) capping layer grafted to MSNs via an acid-cleavable acetal linker, to minimize premature cargo release and provide the nanosystem of pH-responsive drug delivery ability; and ii) a targeting ligand, the plant lectin concanavalin A (ConA), able to selectively recognize, bind and internalize owing to certain cell-surface glycans, such as sialic acids (SA), overexpressed in given tumor cells. This multifunctional nanosystem exhibits a noticeable higher internalization degree into human osteosarcoma cells (HOS), overexpressing SA, compared to healthy preosteoblast cells (MC3T3-E1). Moreover, the results indicate that small DOX loading (2.5 µg mL−1) leads to almost 100% of osteosarcoma cell death in comparison with healthy bone cells, which significantly preserve their viability. Besides, this nanodevice has a cytotoxicity on tumor cells 8-fold higher than that caused by the free drug. These findings demonstrate that the synergistic combination of different building blocks into a unique nanoplatform increases antitumor effectiveness and decreases toxicity towards normal cells. This line of attack opens up new insights in targeted bone cancer therapy. Statement of Significance The development of highly selective and efficient tumor-targeted smart drug delivery nanodevices remains a great challenge in nanomedicine. This work reports the design and optimization of a multifunctional nanosystem based on mesoporous silica nanoparticles (MSNs) featuring selectivity towards human osteosarcoma cells and pH-responsive antitumor drug delivery capability. The novelty and originality of this manuscript relies on proving that the synergistic assembly of different building blocks into a unique nanoplatform increases antitumor effectiveness and decreases toxicity towards healthy cells, which constitutes a new paradigm in targeted bone cancer therapy.Item Concanavalin A-targeted mesoporous silica nanoparticles for infection treatment.(Acta Biomaterialia, 2019) Martínez Carmona, Marina; Izquierdo Barba, Isabel; Colilla Nieto, Montserrat; Vallet Regí, María Dulce NombreThe ability of bacteria to form biofilms hinders any conventional treatment for chronic infections and has serious socio-economic implications. For this purpose, a nanocarrier capable of overcoming the barrier of the mucopolysaccharide matrix of the biofilm and releasing its loadedantibiotic within this matrix would be desirable. Herein, we developed a new nanosystem based on levofloxacin (LEVO)-loaded mesoporous silica nanoparticles (MSNs) decorated with the lectin concanavalin A (ConA). The presence of ConA promotes the internalization of this nanosystem into the biofilm matrix, which increases the antimicrobial efficacy of the antibiotic hosted within the mesopores. This nanodevice is envisioned as a promising alternative to conventional treatments for infection by improving the antimicrobial efficacy and reducing side effects.Item Smart Mesoporous Nanomaterials for Antitumor Therapy(Nanomaterials, 2015) Martínez Carmona, Marina; Colilla Nieto, Montserrat; Vallet Regí, María Dulce NombreThe use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs) exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc.) or external (temperature, light, magnetic field, etc.) stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment.Item A novel visible light responsive nanosystem for cancer treatment(Nanoscale, 2017) Martínez Carmona, Marina; Lozano Borregón, Daniel; Baeza, Alejandro; Colilla Nieto, Montserrat; Vallet Regí, María Dulce NombreA novel singlet-oxygen sensitive drug delivery nanocarrier able to release their cargo after exposure to visible (Vis) light of a common lamp is presented. This nanodevice is based on mesoporous silica nanoparticles (MSN) decorated with porphyrin-caps grafted via reactive oxygen species (ROS)-cleavable linkages. In presence of Vis light the porphyrinnanocaps produce singlet oxygen molecules that break the sensitive-linker, which triggers pore uncapping and therefore allows the release of the entrapped cargo (topotecan, TOP). This new system takes advantage of thE non-toxicity and greater penetration capacity of Vis radiation and a double antitumor effect due to the drug release and the ROS production. In vitro tests with HOS osteosarcoma cancer cells reveal that TOP is able to be released in a controlled fashion inside the tumor cells. This research work constitutes a proof of concept that opens up promising expectations in the seeking for new alternatives for the treatment of cancer.Item A novel zwitterionic bioceramic with dual antibacterial capability(Journal of Materials Chemistry B, 2014) Colilla Nieto, Montserrat; Martínez Carmona, Marina; Sánchez-Salcedo, Sandra; Ruiz González, M. Luisa; González Calbet, José M.; Vallet Regí, María Dulce NombreA novel zwitterionic SBA-15 type bioceramic with dual antibacterial capability has been synthesized. The cocondensation route has been employed to functionalize SBA-15 with primary and secondary amine groups. The resulting material exhibits textural and nanostructural properties comparable to those of pure silica SBA-15, as confirmed by XRD, HR-TEM and N2 adsorption porosimetry. The presence of –NH3 4/–SiO. and >NH2 4/–SiO. zwitterionic pairs on the material surface is evidenced by FTIR and 1H / 13C CP/MAS solid state NMR. The homogeneous distribution of this zwitterionic pairs agrees with the results derived from STEM-EDS studies. z-Potential measurements indicate that the zwitterionic nature of this material is preserved at the physiological pH of 7.4. In vitro bacterial assays using S. aureus demonstrate that the zwitterionic material is capable of inhibiting 99.9% of the bacterial adhesion compared to pure silica SBA-15. Moreover, cephalexin loading and delivery assays indicate that the zwitterionic sample is capable of releasing antibiotic molecules over long time periods. This dual antibacterial capability, i.e. antibiofouling and bactericidal, opens up promising expectations for the treatment of bone implant infections.Item Selective topotecan delivery to cancer cells by targeted pH-sensitive mesoporous silica nanoparticles(RSC Advances, 2016) Martínez Carmona, Marina; Lozano Borregón, Daniel; Colilla Nieto, Montserrat; Vallet Regí, María Dulce NombreTopotecan (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.Item High resolution transmission electron microscopy: A key tool to understand drug release from mesoporous matrices(Microporous and Mesoporous Materials, 2016) Martínez Carmona, Marina; Colilla Nieto, Montserrat; Ruiz González, M. Luisa; González Calbet, José M.; Vallet Regí, María Dulce NombreThis work demonstrates that high resolution transmission electron microscopy (HRTEM) is an essential tool to understand drug delivery performance of mesoporous silica materials, mainly those submitted to functionalization processes involving harsh conditions that may affect the mesostructure. Herein an SBA-15-type mesoporous material bearing Si(CH2)(2)P(O)(OCH2CH3)(2) groups was synthesized following the co-condensation route. Then, the resulting material was treated with 37 wt% HCl to convert ethylphosphonate groups to ethylphosphonic acid groups. The proper dealkylation of ethoxy groups following acid treatment was confirmed by FTIR and CP-MAS H-1 -> C-13 solid state NMR, which indicated the presence of Si(CH2)(2)P(O)(OH)(2) functionalities in the treated sample. Characterization of mesoporous materials by XRD diffraction and N-2 adsorption points to well-ordered SBA-15 structures in both untreated and acid-treated samples. Nonetheless, a deep study by HRTEM reveals that the acid-treatment provokes noticeable loss of mesostructural order, only remaining small crystalline domains. This structural damage does not influence cargo loading but it severely affects the release of molecules confined into the mesopores, as concluded from in vitro delivery tests using cephalexin as model drug. Thus, whereas untreated sample showed a sustained diffusion-controlled drug release during more than 2 weeks, 100% of the loaded drug was released only after 10 h from treated sample. This abrupt burst effect cannot be explained on the basis of the existing matrix-drug interactions, whose nature and extension is quite similar under the release conditions for both samples. Thus, it can be only understood on the basis of the mesostructural damage revealed by HRTEM studies. (C) 2016 Elsevier Inc. All rights reserved.