30 research outputs found
Preparation and Study of the Antibacterial Applications and Oxidative Stress Induction of Copper Maleamate-Functionalized Mesoporous Silica Nanoparticles
Mesoporous silica nanoparticles (MSNs) are an interesting class of nanomaterials with
potential applications in different therapeutic areas and that have been extensively used as drug
carriers in different fields of medicine. The present work is focused on the synthesis of MSNs
containing a maleamato ligand (MSN-maleamic) and the subsequent coordination of copper(II) ions
(MSN-maleamic-Cu) for the exploration of their potential application as antibacterial agents. The
Cu-containing nanomaterials have been characterized by different techniques and the preliminary
antibacterial effect of the supported maleamato-copper(II) complexes has been tested against two
types of bacteria (Gram positive and Gram negative) in different assays to determine the minimum
inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The biological
results showed a moderate antibacterial activity against Escherichia coli which motivated a more
detailed study of the antibacterial mechanism of action of the synthesized maleamate-containing
nanosystems and whose findings showed oxidative stress generation in bacterial cells. All the
prepared nanomaterials were also tested as catalysts in the “solvent free” selective oxidation of
benzyl alcohol, to observe if there is a potential correlation between the catalytic oxidation capacity
of the materials and the observed oxidative stress in bacteria. This may help in the future, for
a more accurate rational design of antibacterial nanosystems, based on their observed catalytic
oxidation activity.This research was funded by Ministerio de Ciencia, Innovación y Universidades Spain-FEDER, grants
number CTQ2015-66164-R and CTQ2017-90802-REDT and by Agencia Nacional de Promoción Científica y
Tecnológica (ANPCyT) (PICT 2015 Nº1558)
Suzuki-Miyaura C-C Coupling Reactions Catalyzed by Supported Pd Nanoparticles for the Preparation of Fluorinated Biphenyl Derivatives
Heterogeneous recyclable catalysts in Suzuki-Miyaura C-C coupling reactions are of great interest in green chemistry as reusable alternatives to homogeneous Pd complexes. Considering the interesting properties of fluorinated compounds for the pharmaceutical industry, as precursors of novel materials, and also as components of liquid crystalline media, this present study describes the preparation of different fluorinated biphenyl derivatives by Suzuki-Miyaura coupling reactions catalyzed by a heterogeneous system (G-COOH-Pd-10) based on Pd nanoparticles supported onto COOH-modified graphene. The catalytic activity of the hybrid material G-COOH-Pd-10 has been tested in Suzuki-Miyaura C–C coupling reactions observing excellent versatility and good conversion rates in the reactions of phenylboronic acid, 4-vinylphenylboronic acid, 4-carboxyphenylboronic acid, and 4-fluorophenylboronic acid with 1-bromo-4-fluorobenzene. In addition, the influence of the arylbromide has been studied by carrying out reactions of 4-fluorophenylboronic acid with 1-bromo-2-fluorobenzene, 1-bromo-3-fluorobenzene, 1-bromo-4-fluorobenzene, 2-bromo-5-fluorotoluene, and 2-bromo-4-fluorotoluene. Finally, catalyst recyclability tests show a good degree of reusability of the system based on G-COOH-Pd-10 as the decrease in catalytic activity after five consecutive catalytic cycles in the reaction of 1-bromo-4-fluorobenzene with 4-florophenylboronic acid at 48 hours of reaction is lower than 8% while in the case of reactions at three hours the recyclability of the systems is much lower.We gratefully acknowledge financial support from the Ministerio de Economía y Competitividad, Spain (Grant no. CTQ2015-66164-R). We would also like to thank Universidad Rey Juan Carlos and Banco de Santander for supporting our Research Group of Excellence QUINANOAP. We would also like to thank Isfahan University of Technology for the partial financial support of the research stay of R.S.E
Anticancer Applications of Nanostructured Silica-Based Materials Functionalized with Titanocene Derivatives: Induction of Cell Death Mechanism through TNFR1 Modulation
A series of cytotoxic titanocene derivatives have been immobilized onto nanostructured silica-based materials using two different synthetic routes, namely, (i) a simple grafting protocol via protonolysis of the Ti-Cl bond; and (ii) a tethering method by elimination of ethanol using triethoxysilyl moieties of thiolato ligands attached to titanium. The resulting nanostructured systems have been characterized by different techniques such as XRD, XRF, DR-UV, BET, SEM, and TEM, observing the incorporation of the titanocene derivatives onto the nanostructured silica and slight changes in the textural features of the materials after functionalization with the metallodrugs. A complete biological study has been carried out using the synthesized materials exhibiting moderate cytotoxicity in vitro against three human hepatic carcinoma (HepG2, SK-Hep-1, Hep3B) and three human colon carcinomas (DLD-1, HT-29, COLO320) and very low cytotoxicity against normal cell lines. In addition, the cells' metabolic activity was modified by a 24-h exposure in a dose-dependent manner. Despite not having a significant effect on TNFα or the proinflammatory interleukin 1α secretion, the materials strongly modulated tumor necrosis factor (TNF) signaling, even at sub-cytotoxic concentrations. This is achieved mainly by upregulation of the TNFR1 receptor production, something which has not previously been observed for these systems.We gratefully acknowledge financial support from FEDER and the Ministerio de Economía
y Competitividad, Spain (grant no. CTQ2015-66164-R) and the Romanian UEFISCDI Exploratory Research
Project PN-III-P4-ID-PCE-2016-0870, IMPRESS.We would also like to thank Universidad Rey Juan Carlos and
Banco de Santander for supporting our Research Group of Excellence QUINANOAP. Finally, we thank D. Pérez
for valuable discussion and S. Carralero and C. Forcé for their assistance with solid-state NMR experiments
Synthesis of a theranostic platform based on fibrous silica nanoparticles for the enhanced treatment of triple-negative breast cancer promoted by a combination of chemotherapeutic agents.
A new series of theranostic silica materials based on fibrous silica particles acting as nanocarriers of two different cytotoxic agents, namely, chlorambucil and an organotin metallodrug have been prepared and structurally characterized. Besides the combined therapeutic activity, these platforms have been decorated with a targeting molecule (folic acid, to selectively target triple negative breast cancer) and a molecular imaging agent (Alexa Fluor 647, to enable their tracking both in vitro and in vivo). The in vitro behaviour of the multifunctional silica systems showed a synergistic activity of the two chemotherapeutic agents in the form of an enhanced cytotoxicity against MDA-MB-231 cells (triple negative breast cancer) as well as by a higher cell migration inhibition. Subsequently, the in vivo applicability of the siliceous nanotheranostics was successfully assessed by observing with in vivo optical imaging techniques a selective tumour accumulation (targeting ability), a marked inhibition of tumour growth paired to a marked antiangiogenic ability after 13 days of systemic administration, thus, confirming the enhanced theranostic activity. The systemic nanotoxicity was also evaluated by analyzing specific biochemical markers. The results showed a positive effect in form of reduced cytotoxicity when both chemotherapeutics are administered in combination thanks to the fibrous silica nanoparticles. Overall, our results confirm the promising applicability of these novel silica-based nanoplatforms as advanced drug-delivery systems for the synergistic theranosis of triple negative breast cancer.We would like to thank the funding of the Ministerio de Ciencia e
Innovación of Spain (former Ministerio de Ciencia Innovación y Universidades of Spain) and FEDER, Una manera de hacer Europa for the
grant number RTI2018-094322-B-I00. We would also like to thank
Comunidad de Madrid for the predoctoral grant PEJD-2017-PRE/BMD3512 (I.M.-P.). M.M, Y.L.M., and M.F. are grateful to the Comunidad
Autónoma de Madrid and FEDER for the I + D collaborative Programme
in Biomedicine NIETO-CM (Project reference B2017-BMD3731). M.F.
and K.O.P. thank the Comunidad Autonoma ´ de Madrid for research
project No. 2017-T1/BIO-4992 (“Atraccion ´ de Talento” Action) cofunded by Universidad Complutense de Madrid. M.F is grateful to Instituto
de Salud Carlos III (ISCIII) for project No DTS20/00109 (AES-ISCIII). M.
M., M.F. and L.L.C would also like to thank Comunidad de Madrid for the
predoctoral grant IND2020/BIO-17523. M.F. and K.O.P. acknowledge
the support of Microscopy & Dynamic Imaging Unit of CNIC, Madrid,
Spain. The Unit is part of the ReDiB-ICTS and has the support of FEDER,
“Una manera de hacer Europa.” The CNIC is supported by the Instituto
de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovacion ´
(MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of
Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/
501100011033).S
Role of Folic Acid in the Therapeutic Action of Nanostructured Porous Silica Functionalized with Organotin(IV) Compounds against Different Cancer Cell Lines
The synthesis, characterization and cytotoxic activity against different cancer cell lines
of various mesoporous silica-based materials containing folate targeting moieties and a cytotoxic
fragment based on a triphenyltin(IV) derivative have been studied. Two different mesoporous
nanostructured silica systems have been used: firstly, micronic silica particles of the MSU-2 type and,
secondly, mesoporous silica nanoparticles (MSNs) of about 80 nm. Both series of materials have been
characterized by different methods, such as powder X-ray diffraction, X-ray fluorescence, absorption
spectroscopy and microscopy. In addition, these systems have been tested against four different cancer
cell lines, namely, OVCAR-3, DLD-1, A2780 and A431, in order to observe if the size of the silica-based
systems and the quantity of incorporated folic acid influence their cytotoxic action. The results show
that the materials are more active when the quantity of folic acid is higher, especially in those cells
that overexpress folate receptors such as OVCAR-3 and DLD-1. In addition, the study of the potential
modulation of the soluble folate receptor alpha (FOLR1) by treatment with the synthesized materials
has been carried out using OVCAR-3, DLD-1, A2780 and A431 tumour cell lines. The results show
that a relatively high concentration of folic acid functionalization of the nanostructured silica together
with the incorporation of the cytotoxic tin fragment leads to an increase in the quantity of the soluble
FOLR1 secreted by the tumour cells. In addition, the studies reported here show that this increase of the soluble FOLR1 occurs presumably by cutting the glycosyl-phosphatidylinositol anchor of
membrane FR-α and by the release of intracellular FR-α. This study validates the potential use of a
combination of mesoporous silica materials co-functionalized with folate targeting molecules and an
organotin(IV) drug as a strategy for the therapeutic treatment of several cancer cells overexpressing
folate receptors.Spanish Government
RTI2018-094322-B-I00
CTQ2017-90802-REDTMinistry of Research and Innovation, CNCS-UEFISCDI within PNCDI III
PN-III-P4-ID-PCCF-2016-014
Dual Anticancer and Antibacterial Properties of Silica-Based Theranostic Nanomaterials Functionalized with Coumarin343, Folic Acid and a Cytotoxic Organotin(IV) Metallodrug
Five different silica nanoparticles functionalized with vitamin B12, a derivative of coumarin found in green plants and a minimum content of an organotin(IV) fragment (1-MSN-Sn, 2-MSN-Sn, 2-SBA-Sn, 2-FSPm-Sn and 2-FSPs-Sn), were identified as excellent anticancer agents against triple negative breast cancer, one of the most diagnosed and aggressive cancerous tumors, with very poor prognosis. Notably, compound 2-MSN-Sn shows selectivity for cancer cells and excellent luminescent properties detectable by imaging techniques once internalized. The same compound is also able to interact with and nearly eradicate biofilms of Staphylococcus aureus, the most common bacteria isolated from chronic wounds and burns, whose treatment is a clinical challenge. 2-MSN-Sn is efficiently internalized by bacteria in a biofilm state and destroys the latter through reactive oxygen species (ROS) generation. Its internalization by bacteria was also efficiently monitored by fluorescence imaging. Since silica nanoparticles are particularly suitable for oral or topical administration, and considering both its anticancer and antibacterial activity, 2-MSN-Sn represents a new dual-condition theranostic agent, based primarily on natural products or their derivatives and with only a minimum amount of a novel metallodrug.We would like to thank funding from RTI2018-094322-B-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, by the “European Union” and the University of the Basque Country UPV/EHU (GIC18/143). M.F. is grateful to Instituto de Salud Carlos III (ISCIII) for project No DTS20/00109 (AES20-ISCIII) and PI22/00789 (AES22-ISCIII). M.F. and K.O.P. acknowledge the support of Microscopy & Dynamic Imaging Unit of CNIC, Madrid, Spain. The Unit is part of the ReDiB-ICTS and has the support of FEDER, “Una manera de hacer Europa.” The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033)
Anticancer Applications and Recent Investigations of Metallodrugs Based on Gallium, Tin and Titanium
For more than 100 years metal complexes have been extensively used in therapy and since the discovery of cisplatin the research in this field has expanded exponentially. The scientific community is always in search of new alternatives to platinum compounds and a wide variety of metallodrugs based on other metals have been reported with excellent therapeutic results. This short review focuses on the work that our research group has carried out since 2007 in collaboration with others and centers on the preparation of organogallium(III) compounds, organotin(IV) derivatives, and titanocene(IV) complexes together with the study of their cytotoxic anticancer properties
Biological Use of Nanostructured Silica-Based Materials Functionalized with Metallodrugs: The Spanish Perspective
Since the pioneering work of Vallet-Regí’s group on the design and synthesis of mesoporous silica-based materials with therapeutic applications, during the last 15 years, the potential use of mesoporous silica nanostructured materials as drug delivery vehicles has been extensively explored. The versatility of these materials allows the design of a wide variety of platforms that can incorporate numerous agents of interest (fluorophores, proteins, drugs, etc.) in a single scaffold. However, the use of these systems loaded with metallodrugs as cytotoxic agents against different diseases and with distinct therapeutic targets has been studied to a much lesser extent. This review will focus on the work carried out in this field, highlighting both the pioneering and recent contributions of Spanish groups that have synthesized a wide variety of systems based on titanium, tin, ruthenium, copper and silver complexes supported onto nanostructured silica. In addition, this article will also discuss the importance of the structural features of the systems for evaluating and modulating their therapeutic properties. Finally, the most interesting results obtained in the study of the potential therapeutic application of these metallodrug-functionalized silica-based materials against cancer and bacteria will be described, paying special attention to preclinical trials in vivo
Biological Use of Nanostructured Silica-Based Materials Functionalized with Metallodrugs: The Spanish Perspective
Since the pioneering work of Vallet-Regí’s group on the design and synthesis of mesoporous silica-based materials with therapeutic applications, during the last 15 years, the potential use of mesoporous silica nanostructured materials as drug delivery vehicles has been extensively explored. The versatility of these materials allows the design of a wide variety of platforms that can incorporate numerous agents of interest (fluorophores, proteins, drugs, etc.) in a single scaffold. However, the use of these systems loaded with metallodrugs as cytotoxic agents against different diseases and with distinct therapeutic targets has been studied to a much lesser extent. This review will focus on the work carried out in this field, highlighting both the pioneering and recent contributions of Spanish groups that have synthesized a wide variety of systems based on titanium, tin, ruthenium, copper and silver complexes supported onto nanostructured silica. In addition, this article will also discuss the importance of the structural features of the systems for evaluating and modulating their therapeutic properties. Finally, the most interesting results obtained in the study of the potential therapeutic application of these metallodrug-functionalized silica-based materials against cancer and bacteria will be described, paying special attention to preclinical trials in vivo
Organotin(IV)-Decorated Graphene Quantum Dots as Dual Platform for Molecular Imaging and Treatment of Triple Negative Breast Cancer.
The pharmacological activity of organotin(IV) complexes in cancer therapy is well recognized but their large applicability is hampered by their poor water solubility. Hence, carbon dots, in particular nitrogen-doped graphene quantum dots (NGQDs), may be a promising alternative for the efficient delivery of organotin(IV) compounds as they have a substantial aqueous solubility, a good chemical stability, and non-toxicity as well as a bright photoluminescence that make them ideal for theranostic applications against cancer. Two different multifunctional nanosystems have been synthesized and fully characterized based on two fragments of organotin-based cytotoxic compounds and 4-formylbenzoic acid (FBA), covalently grafted onto the NGQDs surface. Subsequently, an in vitro determination of the therapeutic and theranostic potential of the achieved multifunctional systems was carried out. The results showed a high cytotoxic potential of the NGQDs-FBA-Sn materials against breast cancer cell line (MDA-MB-231) and a lower effect on a non-cancer cell line (kidney cells, HEK293T). Besides, thanks to their optical properties, the dots enabled their fluorescence molecular imaging in the cytoplasmatic region of the cells pointing towards a successful cellular uptake and a release of the metallodrug inside cancer cells (NGQDs-FBA-Sn).This work was supported by Operational Program Research,
Development, and Education-Project ‘MSCAfellow4@MUNI’ (No.
CZ.02.2.69/0.0/0.0/20_079/0017045) and the Spanish Ministry of
Universities for a Maria Zambrano funding (RSU.UDC.MZ09)
transferred by the European Union-Next Generation EU. We
acknowledge CzechNanoLab Research Infrastructure
(LM2018110), supported by the Ministry of Education, Youth
and Sports of the Czech Republic (MEYS CR). We are grateful to
Prof. Vladimír Šindelář and Prof. Petr Klan for allowing us to use
the MW reactor, UV-vis and fluorescence spectrometer, supported by RECETOX research infrastructure (via MEYS CR under
LM2018121). M.F. is grateful to Instituto de Salud Carlos III
(ISCIII) for project No DTS20/00109 (AES20-ISCIII) and PI22/
00789 (AES22-ISCIII). M.F. and K.O.P. acknowledge the support
of Microscopy & Dynamic Imaging Unit of CNIC, Madrid, Spain.
The Unit is part of the ReDiB-ICTS and has the support of FEDER,
“Una manera de hacer Europa.” The CNIC is supported by the
Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e
Innovación (MCIN) and the Pro CNIC Foundation, and is a
Severo Ochoa Center of Excellence (grant CEX2020-001041-S
funded by MICIN/AEI/10.13039/501100011033). We would also
like to thank funding from the research project PID2022-
136417NB-I00 financed by MCIN/AEI/10.13039/501100011033/
and “ERDF A way of making Europe”, and from the Research
Thematic Network RED2022-134091-T financed by MCIN/AEI/
10.13039/501100011033.S