17 research outputs found
Applications of Nanomaterials Based on Magnetite and Mesoporous Silica on the Selective Detection of Zinc Ion in Live Cell Imaging
Functionalized magnetite nanoparticles (FMNPs) and functionalized mesoporous silica
nanoparticles (FMSNs) were synthesized by the conjugation of magnetite and mesoporous silica with
the small and fluorogenic benzothiazole ligand, that is, 2(2-hydroxyphenyl)benzothiazole (hpbtz).
The synthesized fluorescent nanoparticles were characterized by FTIR, XRD, XRF, 13C CP MAS
NMR, BET, and TEM. The photophysical behavior of FMNPs and FMSNs in ethanol was studied
using fluorescence spectroscopy. The modification of magnetite and silica scaffolds with the highly
fluorescent benzothiazole ligand enabled the nanoparticles to be used as selective and sensitive optical
probes for zinc ion detection. Moreover, the presence of hpbtz in FMNPs and FMSNs induced efficient
cell viability and zinc ion uptake, with desirable signaling in the normal human kidney epithelial
(Hek293) cell line. The significant viability of FMNPs and FMSNs (80% and 92%, respectively)
indicates a potential applicability of these nanoparticles as in vitro imaging agents. The calculated
limit of detections (LODs) were found to be 2.53 X 10-6 and 2.55 X 10-6 M for Fe3O4-H@hpbtz and
MSN-Et3N-IPTMS-hpbtz-f1, respectively. FMSNs showed more pronounced zinc signaling relative
to FMNPs, as a result of the more efficient penetration into the cells.This research was funded by several sources. The URJC authors thank the financial
support of theMinisterio de Economía y Competitividad and FEDER (Grants nos. CTQ2015-66164-R and
CTQ2017-90802-REDT) and Universidad Rey Juan Carlos-Banco de Santander for supporting our excellence
group QUINANOAP. The partial support of this work by the Isfahan University of Technology Research Council
(grant number 500/95/24305 and the Iran National Science Foundation through INSF grant number 95828071 is
also acknowledged. The CNIC is supported by the Spanish Ministerio de Ciencia, Innovación y Universidades
and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505). M.F. would like to
thank MEyC for the research grant no. SAF2014-59118-JIN, co-funded by Fondo Europeo de Desarrollo Regional
(FEDER) and COST Action CA1520: ‘European Network on NMR Relaxometry-EURELAX’. M.F. would also like
to thank the Community of Madrid for research contract num. 2017-T1/BIO-4992 (‘Atraccion de Talento’ Action)
cofunded by Universidad Complutense de Madrid
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)
NIL10: A New IL10-Receptor Binding Nanoparticle That Induces Cardiac Protection in Mice and Pigs Subjected to Acute Myocardial Infarction through STAT3/NF-kB Activation.
Background: Early response after acute myocardial infarction (AMI) prevents extensive
cardiac necrosis, in which inflammation resolution, including expression of anti-inflammatory
interleukin-10 (IL-10), may play a key role. (2) Methods: We synthesized NIL10, a micelle-based
nanoparticle, to target IL-10 receptor in mice and pigs subjected to AMI. (3) Results: Administration
of NIL10 induced cardiac protection of wild-type and IL-10 knockout mice and pigs subjected to AMI.
Cardiac protection was not induced in IL-10-receptor null mice, as shown by a significant recovery of
cardiac function, in which inflammatory foci and fibrosis were strongly reduced, together with the
finding that resolving M2-like macrophage populations were increased after day 3 of reperfusion. In
addition, anti-inflammatory cytokines, including IL-4, IL-7, IL-10, IL-13, IL-16, and IL-27 were also
elevated. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway,
and STAT3-dependent inhibition of nuclear translocation of pro-inflammatory NF-kB transcription
factor. (4) Conclusions: Taken together, we propose using NIL10 as a novel therapeutic tool against
AMI-induced cardiac damagepost-print4711 K
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
Recent Advances in Multimodal Molecular Imaging of Cancer Mediated by Hybrid Magnetic Nanoparticles
Cancer is the second leading cause of death in the world, which is why it is so important to make an early and very precise diagnosis to obtain a good prognosis. Thanks to the combination of several imaging modalities in the form of the multimodal molecular imaging (MI) strategy, a great advance has been made in early diagnosis, in more targeted and personalized therapy, and in the prediction of the results that will be obtained once the anticancer treatment is applied. In this context, magnetic nanoparticles have been positioned as strong candidates for diagnostic agents as they provide very good imaging performance. Furthermore, thanks to their high versatility, when combined with other molecular agents (for example, fluorescent molecules or radioisotopes), they highlight the advantages of several imaging techniques at the same time. These hybrid nanosystems can be also used as multifunctional and/or theranostic systems as they can provide images of the tumor area while they administer drugs and act as therapeutic agents. Therefore, in this review, we selected and identified more than 160 recent articles and reviews and offer a broad overview of the most important concepts that support the synthesis and application of multifunctional magnetic nanoparticles as molecular agents in advanced cancer detection based on the multimodal molecular imaging approach
Ionotropic Gelation-Based Synthesis of Chitosan-Metal Hybrid Nanoparticles Showing Combined Antimicrobial and Tissue Regenerative Activities
The treatment of skin wounds poses significant clinical challenges, including the risk of bacterial infection. In particular due to its antimicrobial and tissue regeneration abilities chitosan (a polymeric biomaterial obtained by the deacetylation of chitin) has received extensive attention for its effectiveness in promoting skin wound repair. On the other hand, due to their intrinsic characteristics, metal nanoparticles (e.g., silver (Ag), gold (Au) or iron oxide (Fe3O4)) have demonstrated therapeutic properties potentially useful in the field of skin care. Therefore, the combination of these two promising materials (chitosan plus metal oxide NPs) could permit the achievement of a promising nanohybrid with enhanced properties that could be applied in advanced skin treatment. In this work, we have optimized the synthesis protocol of chitosan/metal hybrid nanoparticles by means of a straightforward synthetic method, ionotropic gelation, which presents a wide set of advantages. The synthesized hybrid NPs have undergone to a full physicochemical characterization. After that, the in vitro antibacterial and tissue regenerative activities of the achieved hybrids have been assessed in comparison to their individual constituent. As result, we have demonstrated the synergistic antibacterial plus the tissue regeneration enhancement of these nanohybrids as a consequence of the fusion between chitosan and metallic nanoparticles, especially in the case of chitosan/Fe3O4 hybrid nanoparticles
Ionotropic Gelation-Based Synthesis of Chitosan-Metal Hybrid Nanoparticles Showing Combined Antimicrobial and Tissue Regenerative Activities
The treatment of skin wounds poses significant clinical challenges, including the risk of bacterial infection. In particular due to its antimicrobial and tissue regeneration abilities chitosan (a polymeric biomaterial obtained by the deacetylation of chitin) has received extensive attention for its effectiveness in promoting skin wound repair. On the other hand, due to their intrinsic characteristics, metal nanoparticles (e.g., silver (Ag), gold (Au) or iron oxide (Fe3O4)) have demonstrated therapeutic properties potentially useful in the field of skin care. Therefore, the combination of these two promising materials (chitosan plus metal oxide NPs) could permit the achievement of a promising nanohybrid with enhanced properties that could be applied in advanced skin treatment. In this work, we have optimized the synthesis protocol of chitosan/metal hybrid nanoparticles by means of a straightforward synthetic method, ionotropic gelation, which presents a wide set of advantages. The synthesized hybrid NPs have undergone to a full physicochemical characterization. After that, the in vitro antibacterial and tissue regenerative activities of the achieved hybrids have been assessed in comparison to their individual constituent. As result, we have demonstrated the synergistic antibacterial plus the tissue regeneration enhancement of these nanohybrids as a consequence of the fusion between chitosan and metallic nanoparticles, especially in the case of chitosan/Fe3O4 hybrid nanoparticles.Comunidad de MadridFederación Española de Enfermedades RarasUniversidad Complutense de MadridInstituto de Salud Carlos IIICentro Nacional de Investigaciones CardiovascularesMinisterio de Economía, Comercio y Empresa (España)Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaTRUEpu
Hybrid Decorated Core@Shell Janus Nanoparticles as a Flexible Platform for Targeted Multimodal Molecular Bioimaging of Cancer
In the recent years, targeted cancer theranosis, the concomitant therapeutic treatment and selective visualization of cancerous tissue, has become a powerful strategy to improve patient prognosis. In this context, targeted multimodal molecular imaging, the combination of different imaging modalities overcoming their individual limitations, has
attracted great attention. Due to their unique properties, advanced nanomaterials have taken center stage in the development of theranostics. In this work, we report a novel
Janus nanoplatform by combining an Fe3O4 NPs/mesoporous silica core@shell face together with an Au nanoparticle face. Due to its anisotropy, this hybrid nanomaterial enabled the orthogonal site-selective modification of each face permitting the incorporation of a targeting peptide for cancer detection (cRGD) and a fluorescent dye. Due to the intrinsic characteristics of this Janus nanoplatform together with those selectively generated on their surfaces, the resulting hybrid nanocarrier successfully promoted the in vivo tumor-targeted multimodal imaging by magnetic resonance (Fe3O4 core), computed tomography (AuNP face), and fluorescent tracking (fluorescent dye loading) in a fibrosarcoma-bearing mouse model. The achieved results endorse these hybrid Janus nanoparticles as a powerful and flexible platform with integrated imaging and carrier functionalities to be equipped with therapeutic features to generate an advanced multifunctional nanocarrier for targeted cancer theranosis.Severo Ochoa Center of ExcellenceMinisterio de Economia y CompetitividadComunidad Autonoma de MadridMinisterio de Economia y ́CompetitividadComunidad de Madrid Projects, Programme NANOAVANSENSI + D collaborative Programme in Biomedicine NIETO-CMDepto. de Química AnalíticaFac. de Ciencias QuímicasTRUEpu