Person:
Colilla Nieto, Montserrat

First Name

Montserrat

Last Name

Colilla Nieto

URI

https://hdl.handle.net/20.500.14352/77764

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Química en Ciencias Farmacéuticas

Area

Química Inorgánica

Identifiers

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Search Results

Now showing 1 - 10 of 16

Preventing bacterial adhesion on scaffolds for bone tissue engineering
(International Journal of Bioprinting, 2016) Sánchez Salcedo, Sandra; Colilla Nieto, Montserrat; Izquierdo Barba, Isabel; Vallet Regí, María Dulce Nombre
Bone implant infection constitutes a major sanitary concern which is associated to high morbidity and health costs. This manuscript focused on overviewing the main research efforts committed up to date to develop innovative alternatives to conventional treatments, such as those with antibiotics. These strategies mainly rely on chemical modifi-cations of the surface of biomaterials, such as providing it of zwitterionic nature, and tailoring the nanostructure surface of metal implants. These surface modifications have successfully allowed inhibition of bacterial adhesion, which is the first step to implant infection, and preventing long-term biofilm formation compared to pristine materials. These strate-gies could be easily applied to provide three-dimensional (3D) scaffolds based on bioceramics and metals, of which its manufacture using rapid prototyping techniques was reviewed. This opens the gates for the design and development of advanced 3D scaffolds for bone tissue engineering to prevent bone implant infections. Keywords: Antibacterial adhesion, biofilm formation, zwitterionic surfaces, nanostructured surfaces, rapid prototyping 3D scaffolds, bone tissue engineering.
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 Nombre
A 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.
Recent advances in mesoporous silica nanoparticles for antitumor therapy: our contribution
(Biomaterials Science, 2016) Baeza García, Alejandro; Manzano García, Miguel; Colilla Nieto, Montserrat; Vallet Regí, María Dulce Nombre
Since 2001, when our research group proposed for the first time MCM-41 as a drug release system, the scientific community has demonstrated a growing interest in mesoporous silica nanoparticles (MSNs) for their revolutionary potential in nanomedicine. Among the diverse pathologies that can be treated with MSNs, cancer has received increasing attention. MSNs can be loaded with large amounts of therapeutic cargoes and once intravenously administrated preferentially accumulate in solid tumours via the enhanced permeation and retention (EPR) effect. Herein we report the recent developments achieved by our research group as a pioneer in this field, highlighting: the design of sophisticated MSNs as stimuli-responsive drug delivery systems to release the entrapped cargo upon exposure to a given stimulus while preventing the premature release of highly cytotoxic drugs before reaching the target; transporting non-toxic prodrugs and the enzyme responsible for its conversion into cytotoxic agents into the same MSNs; improving the selectivity and cellular uptake by cancer cells by active targeting of MSNs; increasing the penetration of MSNs within the tumour mass, which is one of the major challenges in the use of NPs to treat solid tumours.
Amine-Functionalized Mesoporous Silica Nanoparticles: A New Nanoantibiotic for Bone Infection Treatment
(Biomedical Glasses, 2018) Pedraza, Daniel; Díez, Jaime; Izquierdo Barba, Isabel; Colilla Nieto, Montserrat; Vallet Regí, María Dulce Nombre
This manuscript reports an effective new alternative for the management of bone infection by the 5 development of an antibiotic nanocarrier able to penetrate bacterial biofilm, thus enhancing antimicrobial effectiveness. This nanosystem, also denoted as “nanoantibiotic”, consists in mesoporous silica nanoparticles (MSNs) loaded with an antimicrobial agent (levofloxacin, LEVO) 10 and externally functionalized with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (DAMO) as targeting agent. This amine functionalization provides MSNs of positive charges, which improves the affinity towards the negatively charged bacteria wall and biofilm. Physical and 15 chemical properties of the nanoantibiotic were studied using different characterization techniques, including Xray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption porosimetry, elemental chemical analysis, dynamic light scattering (DLS), zeta (� )-potential 20 and solid-state nuclear magnetic resonance (NMR). “In vial” LEVO release profiles and the in vitro antimicrobial effectiveness of the different released doses were investigated. The efficacy of the nanoantibiotic against a S. aureus biofilm was also determined, showing the practically total 25 destruction of the biofilmdue to the high penetration ability of the developed nanosystem. These findings open up promising expectations in the field of bone infection treatment.
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 Nombre
The 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.
Advances in mesoporous silica-based nanocarriers for co-delivery and combination therapy against cancer
(Expert Opinion on Drug Delivery, 2016) Castillo Romero, Rafael; Colilla Nieto, Montserrat; Vallet Regí, María Dulce Nombre
Introduction: Nanocarriers have emerged as a powerful alternative for cancer therapy.Indeed, they are promising candidates to tackle the acquired resistance of surviving cells against antiproliferative drugs – the so-called multidrug resistance (MDR) phenomenon – which has arisen as one of the major clinical issues of chemotherapy. Among nanocarriers, this review focuses on the recent approaches based on tailored mesoporous silica nanoparticles (MSNs) that could overcome this problem. Areas covered: Herein we summarize the current efforts developed to provide MSNbased nanosystems of enhanced dual therapeutic action against diseased cells. This can be accomplished by three main approaches: i) increasing nanosystems’ killing capability towards particular cells by enhancing both recognition and specificity; ii)increasing the apoptotic effect throughout co-delivery of several drugs; or iii)combining drug delivery with apoptosis induced by physical methods. Expert Opinion: The development of multifunctional nanosystems able to exert the optimal therapeutic action through the minimal administration constitutes a major challenge in nanomedicine. Recent developments in advanced MSN-based platforms for drug delivery represent promising avenues in the management of MDR associated with cancer therapy. All strategies discussed in this manuscript demonstrate improvements against difficult-to-treat tumors.
Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery
(Expert Opinion on Drug Delivery, 2015) Baeza, Alejandro; Colilla Nieto, Montserrat; Varas Muriel, María José; Vallet Regí, María Dulce Nombre
Mesoporous silica nanoparticles (MSNPs)are one of the most promising inorganic drug delivery systems(DDSs). The design and development of tumour-targeted MSNPs with stimuli-responsive drug release capability aim at enhancing the efficiency and minimising the side effects of antitumour drugs for cancer therapy.
Zwitterionic ceramics for biomedical applications
(Acta Biomaterialia, 2016) Izquierdo Barba, Isabel; Colilla Nieto, Montserrat; Vallet Regí, María Dulce Nombre
Bioceramics for bone tissue regeneration, local drug delivery and nanomedicine, are receiving growing attention by the biomaterials scientific community. The design of bioceramics with improved surface properties able to overcome clinical issues is a great scientific challenge. Zwitterionization of surfaces has arisen as a powerful alternative in the design of biocompatible bioceramics capable to inhibit bacterial and non-specific protein adsorption, which opens up new insights into the biomedical applications of these materials. This manuscript reviews the different approaches reported up to date for the synthesis and characterization of zwitterionic bioceramics with potential clinical applications. Statement of Significance Zwitterionic bioceramics are receiving growing attention by the biomaterials scientific community due to their great potential in bone tissue regeneration, local drug delivery and nanomedicines. Herein, the different strategies developed so far to synthesize and characterize zwitterionic bioceramics with potential clinical applications are summarized. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Smart Mesoporous Nanomaterials for Antitumor Therapy
(Nanomaterials, 2015) Martínez Carmona, Marina; Colilla Nieto, Montserrat; Vallet Regí, María Dulce Nombre
The 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.
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 Nombre
A 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.