Publication:
Molecular gates in mesoporous bioactive glasses for the treatment of bone tumors and infection

Research Projects
Organizational Units
Journal Issue
Abstract
Silica mesoporous nanomaterials have been proved to have meaningful application in biotechnology and biomedicine. Particularly, mesoporous bioactive glasses are recently gaining importance thanks to their bone regenerative properties. Moreover, the mesoporous nature of these materials makes them suitable for drug delivery applications, opening new lines in the field of bone therapies. In this work, we have developed innovative nanodevices based on the implementation of adenosine triphosphate (ATP) and e-poly-l-lysine molecular gates using a mesoporous bioglass as an inorganic support. The systems have been previously proved to work properly with a fluorescence probe and subsequently with an antibiotic(levofloxacin) and an antitumoral drug(doxorubicin). The bioactivity of the prepared materials has also been tested, giving promising results. Finally, in vitro cell culture studies have been carried out; demonstrating that this gated devices can provide useful approaches for bone cancer and bone infection treatments. Statement of Significance Molecular-gated materials have recently been drawing attention due to their applications in fields as biomedicine and molecular recognition. For the first time as we are aware, we report herein a new enzymatic responsive molecular-gated device consisting in a mesoporous bioactive glass support implemented with two different molecular gates. Both controlled drug delivery properties and apatite-like phase formation ability of the device have been demonstrated, getting promising results. This approach opens up the possibility of developing new stimuli-responsive tailored biomaterials for bone cancer and infection treatments as well as regenerative bone grafts.
Description
RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí)
Keywords
Citation
D. Arcos, M. Vallet-Regí, Sol-gel silica-based biomaterials and bone tissue regeneration, Acta Biomater. 6 (2010) 2874–2888. [2] C. Wu, J. Chang, Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application, Interface Focus. 2 (2012) 292–306. [3] L.L. Hench, J.M. Polak, Third-generation biomedical materials, Science 295 (2002) 1014–1017. [4] I. Izquierdo-Barba, D. Arcos, Y. Sakamoto, O. Terasaki, A. López-Noriega, M. Vallet-Regí, High-performance mesoporous bioceramics mimicking bone mineralization, Chem. Mater. 20 (2008) 3191–3198. [5] X. Yan, C. Yu, X. Zhou, J. Tang, D. Zhao, Highly ordered mesoporous bioactive glasses with superior in vitro bone-forming bioactivities, Angew. Chemie - Int. Ed. 43 (2004) 5980–5984. [6] M. Vallet-Regí, F. Balas, D. Arcos, Mesoporous materials for drug delivery, Angew. Chem. Int. Ed. Engl. 46 (2007) 7548–7558. [7] F. Balas, M. Manzano, P. Horcajada, M. Vallet-Regí, Confinement and controlled release of bisphosphonates on ordered mesoporous silica-based materials, J. Am. Chem. Soc. 128 (2006) 8116–8117. [8] D.P. Ferris, Y.L. Zhao, N.M. Khashab, H.A. Khatib, J.F. Stoddart, J.I. Zink, Lightoperated mechanized nanoparticles, J. Am. Chem. Soc. 131 (2009) 1686–1688. [9] C. Wu, J. Chang, Multifunctional mesoporous bioactive glasses for effective delivery of therapeutic ions and drug/growth factors, J. Control. Release 193 (2014) 282–295. [10] A. López-Noriega, D. Arcos, M. Vallet-Regí, Functionalizing mesoporous bioglasses for long-term anti-osteoporotic drug delivery, Chem. - A Eur. J. 16 (2010) 10879–10886. [11] E. Aznar, R. Martínez-Máñez, F. Sancenón, Controlled release using mesoporous materials containing gate-like scaffoldings, Expert Opin. Drug Deliv. 6 (2009) 643–655. [12] C. Giménez, C. de la Torre, M. Gorbe, E. Aznar, F. Sancenón, J.R. Murguía, R. Martínez-Máñez, M.D. Marcos, P. Amorós, Gated mesoporous silica nanoparticles for the controlled delivery of drugs in cancer cells, Langmuir 31 (2015) 3753–3762. [13] E. Aznar, M. Oroval, L. Pascual, J.R. Murguía, R. Martínez-Máñez, F. Sancenón, Gated Materials for On-Command Release of Guest Molecules, Chem. Rev. 116 (2016) 561–718. [14] C. Coll, A. Bernardos, R. Martínez-Máñez, F. Sancenón, Gated silica mesoporous supports for controlled release and signaling applications, Acc. Chem. Res. 46 (2013) 339–349. [15] M. Manzano, M. Vallet-Regí, New developments in ordered mesoporous materials for drug delivery, J. Mater. Chem. 20 (2010) 5593–5604. [16] E. Aznar, R. Villalonga, C. Giménez, F. Sancenón, M.D. Marcos, R. Martínez- Máñez, P. Díez, J.M. Pingarrón, P. Amorós, Glucose-triggered release using enzyme-gated mesoporous silica nanoparticles, Chem. Commun. (Camb.) 49 (2013) 6391–6393. [17] X. Sun, Y. Zhao, V.S.Y. Lin, I.I. Slowing, B.G. Trewyn, Luciferase and luciferin coimmobilized mesoporous silica nanoparticle materials for intracellular biocatalysis, J. Am. Chem. Soc. 133 (2011) 18554–18557. [18] R. Liu, X. Zhao, T. Wu, P. Feng, Tunable redox-responsive hybrid nanogated ensembles, J. Am. Chem. Soc. 130 (2008) 14418–14419. [19] R. Liu, Y. Zhang, X. Zhao, A. Agarwal, L.J. Mueller, P. Feng, PH-responsive nanogated ensemble based on gold-capped mesoporous silica through an acidlabile acetal linker, J. Am. Chem. Soc. 132 (2010) 1500–1501. [20] A. Bernardos, E. Aznar, C. Coll, R. Martínez-Máñez, J.M. Barat, M.D. Marcos, F. Sancenón, A. Benito, J. Soto, Controlled release of vitamin B2 using mesoporous materials functionalized with amine-bearing gate-like scaffoldings, J. Control. Release 131 (2008) 181–189. [21] N. Mas, I. Galiana, S. Hurtado, L. Mondragón, A. Bernardos, F. Sancenón, M.D. Marcos, P. Amorós, N. Abril-Utrillas, R. Martínez-Máñez, J.R. Murguía, Enhanced antifungal efficacy of tebuconazole using gated pH-driven mesoporous nanoparticles, Int. J. Nanomedicine. 9 (2014) 2597–2606. [22] J.L. Paris, M.V. Cabanas, M. Manzano, M. Vallet-Regí, Polymer-Grafted Mesoporous Silica Nanoparticles as Ultrasound-Responsive Drug Carriers, ACS Nano 9 (2015) 11023–11033. [23] N.K. Mal, M. Fujiwara, Y. Tanaka, T. Taguchi, M. Matsukata, Photo-switched storage and release of guest molecules in the pore void of coumarin-modified MCM-41, Chem. Mater. 15 (2003) 3385–3394. [24] D. Tarn, D.P. Ferris, J.C. Barnes, M.W. Ambrogio, J.F. Stoddart, J.I. Zink, A reversible light-operated nanovalve on mesoporous silica nanoparticles, Nanoscale. 6 (2014) 3335–3343. [25] A. Schlossbauer, S. Warncke, P.M.E. Gramlich, J. Kecht, A. Manetto, T. Carell, T. Bein, A programmable DNA-based molecular valve for colloidal mesoporous silica, Angew. Chem. Int. Ed. Engl. 49 (2010) 4734–4737. [26] Z. Yu, N. Li, P. Zheng, W. Pan, B. Tang, Temperature-responsive DNA-gated nanocarriers for intracellular controlled release, Chem. Commun. (Camb.) 50 (2014) 3494–3497. [27] L. Mondragón, N. Mas, V. Ferragud, C. de la Torre, A. Agostini, R. Martínez- Máñez, F. Sancenón, P. Amorós, E. Pérez-Payá, M. Orzáez, Enzyme-responsive intracellular-controlled release using silica mesoporous nanoparticles capped with E-poly-L-lysine, Chemistry. 20 (2014) 5271–5281. [28] Z. Zhang, D. Balogh, F. Wang, I. Willner, Smart mesoporous SiO2 nanoparticles for the DNAzyme-induced multiplexed release of substrates, J. Am. Chem. Soc. 135 (2013) 1934–1940. [29] Z. Zhang, F. Wang, D. Balogh, I. Willner, PH-controlled release of substrates from mesoporous SiO2 nanoparticles gated by metal ion-dependent DNAzymes, J. Mater. Chem. B. 2 (2014) 4449–4455. [30] Y.-L. Sun, Y. Zhou, Q.-L. Li, Y.-W. Yang, Enzyme-responsive supramolecular nanovalves crafted by mesoporous silica nanoparticles and cholinesulfonatocalix[ 4]arene [2]pseudorotaxanes for controlled cargo release, Chem. Commun. (Camb.) 49 (2013) 9033–9035. [31] F. Porta, G.E.M. Lamers, J. Morrhayim, A. Chatzopoulou, M. Schaaf, H. den Dulk, C. Backendorf, J.I. Zink, A. Kros, Folic Acid-Modified Mesoporous Silica Nanoparticles for Cellular and Nuclear Targeted Drug Delivery, Adv. Healthc. Mater. 2 (2013) 281–286. [32] C. de la Torre, I. Casanova, G. Acosta, C. Coll, M.J. Moreno, F. Albericio, E. Aznar, R. Mangues, M. Royo, F. Sancenón, R. Martínez-Máñez, Gated mesoporous silica nanoparticles using a double-role circular peptide for the controlled and target-preferential release of doxorubicin in CXCR4-expresing lymphoma cells, Adv. Funct. Mater. 25 (2014) 687–695. [33] C. Coll, L. Mondragón, R. Martínez-Máñez, F. Sancenón, M.D. Marcos, J. Soto, P. Amorós, E. Pérez-Payá, Enzyme-mediated controlled release systems by anchoring peptide sequences on mesoporous silica supports, Angew. Chemie - Int. Ed. 50 (2011) 2138–2140. [34] A. Ultimo, C. Giménez, P. Bartovsky, E. Aznar, F. Sancenón, M.D. Marcos, P. Amorós, A.R. Bernardo, R. Martínez-Máñez, A.M. Jiménez-Lara, J.R. Murguía, Targeting Innate Immunity with dsRNA-Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells, Chemistry. 22 (2016) 1582–1586. [35] B.G. Trewyn, S. Giri, I.I. Slowing, V.S.-Y. Lin, Mesoporous silica nanoparticle based controlled release, drug delivery, and biosensor systems, Chem. Commun. (Camb.) (2007) 3236–3245. [36] H.M. Lin, W.K. Wang, P.A. Hsiung, S.G. Shyu, Light-sensitive intelligent drug delivery systems of coumarin-modified mesoporous bioactive glass, Acta Biomater. 6 (2010) 3256–3263. [37] N. Mas, D. Arcos, L. Polo, E. Aznar, S. Sánchez-Salcedo, F. Sancenón, A. García, M.D. Marcos, A. Baeza, M. Vallet-Regí, R. Martínez-Máñez, Towards the development of smart 3D ‘‘gated scaffolds” for on-command delivery, Small 10 (2014) 4859–4864. [38] N. Gómez-Cerezo, I. Izquierdo-Barba, D. Arcos, M. Vallet-Regí, Tailoring the biological response of mesoporous bioactive materials, J. Mater. Chem. B. 3 (2015) 3810–3819. [39] M.P. Nandakumar, A. Cheung, M.R. Marten, Proteomic analysis of extracellular proteins from Escherichia coli W3110, J. Proteome Res. 5 (2006) 1155–1161. [40] K. Haddadi, F. Moussaoui, I. Hebia, F. Laurent, Y. Le Roux, E. coli proteolytic activity in milk and casein breakdown, Reprod. Nutr. Dev. 45 (2005) 485–496. [41] G. Bacci, A. Longhi, S. Ferrari, S. Lari, M. Manfrini, D. Donati, C. Forni, M. Versari, Prognostic significance of serum alkaline phosphatase in osteosarcoma of the extremity treated with neoadjuvant chemotherapy: Recent experience at Rizzoli Institute, Oncol. Rep. 9 (2002) 171–175. [42] I. Trenda, Á. Szegedi, K. Yoncheva, P. Shestakova, J. Mihály, A. Risti, S. Konstantinov, M. Popova, A pH dependent delivery of mesalazine from polymer coated and drug-loaded SBA-16 systems, Eur. J. Pharm. Sci. 81 (2016) 75–81. [43] M.J. Potrzebowski, J. Gajda, W. Ciesielski, I.M. Montesinos, Distance measurements in disodium ATP hydrates by means of 31P double quantum two-dimensional solid-state NMR spectroscopy, J. Magn. Reson. 179 (2006) 173–181. [44] U.A. Hellmich, W. Haase, S. Velamakanni, H.W. van Veen, C. Glaubitz, Caught in the Act: ATP hydrolysis of an ABC-multidrug transporter followed by real-time magic angle spinning NMR, FEBS Lett. 582 (2008) 3557–3562. [45] S. Huh, J.W. Wiench, J. Yoo, M. Pruski, V.S. Lin, Organic Functionalization and Morphology Control of Mesoporous Silicas via a Co-Condensation Synthesis Method, Chem. Mater. 15 (2003) 4247–4256. [46] M.R. Filgueiras, G.P. La Torre, L.L. Hench, Solution effects on the surface reactions of a bioactive glass, J. Biomed. Mater. Res. 27 (1993) 445–453. [47] O.P. Filho, G.P. La Torre, L.L. Hench, Effect of crystallization on apatite-layer formation of bioactive glass 45S5, J. Biomed. Mater. Res. 30 (1996) 509–514. 12 L. Polo et al. / Acta Biomaterialia xxx (2017) xxx–xxx Please cite this article in press as: L. Polo et al., Molecular gates in mesoporous bioactive glasses for the treatment of [48] T. Kokubo, H. Kushitani, S. Sakka, T. Kitsugi, T. Yamamuro, Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W3, J. Biomed. Mater. Res. 24 (1990) 721–734. [49] L.L. Hench, Biomaterials, Science 208 (1980) 826–831. [50] C. Turdean-Ionescu, B. Stevensson, I. Izquierdo-Barba, A. García, D. Arcos, M. Vallet-Regí, M. Edén, Surface Reactions of Mesoporous Bioactive Glasses Monitored by Solid-State NMR: Concentration Effects in Simulated Body Fluid, J. Phys. Chem. C 120 (2016) 4961–4974. [51] R. Mathew, C. Turdean-Ionescu, B. Stevensson, I. Izquierdo-Barba, A. García, D. Arcos, M. Vallet-Regí, M. Edén, Direct probing of the phosphate-ion distribution in bioactive silicate glasses by solid-state NMR: Evidence for transitions between random/clustered scenarios, Chem. Mater. 25 (2013) 1877–1885. [52] A. García,M. Cicuéndez, I. Izquierdo-Barba, D. Arcos,M. Vallet-Regí, Essential Role of Calcium Phosphate Heterogeneities in 2D-Hexagonal and 3D-Cubic SiO 2 �CaO�P 2O5Mesoporous BioactiveGlasses,Chem.Mater. 21 (2009) 5474–5484. [53] E. Leonova, I. Izquierdo-Barba, D. Arcos, A. López-Noriega, N. Hedin, M. Vallet- Regí, M. Edén, Multinuclear Solid-State NMR Studies of Ordered Mesoporous Bioactive Glasses, J. Phys. Chem. C 112 (2008) 5552–5562. [54] T. Yoshida, T. Nagasawa, Epsilon-Poly-L-lysine: microbial production, biodegradation and application potential, Appl. Microbiol. Biotechnol. 62 (2003) 21–26.
Collections