Chromogenic Chemodosimeter Based on Capped Silica Particles to Detect Spermine and Spermidine
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nanomaterials Article Chromogenic Chemodosimeter Based on Capped Silica Particles to Detect Spermine and Spermidine Mariana Barros 1, Alejandro López-Carrasco 1, Pedro Amorós 2,* , Salvador Gil 1,3 , Pablo Gaviña 1,3 , Margarita Parra 1,3, Jamal El Haskouri 2, Maria Carmen Terencio 1,4 and Ana M. Costero 1,3,* 1 Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitad Politècnica de València, Universitat de València, Doctor Moliner 50, Burjassot, 46100 Valencia, Spain; [email protected] (M.B.); [email protected] (A.L.-C.); [email protected] (S.G.); [email protected] (P.G.); [email protected] (M.P.); [email protected] (M.C.T.) 2 Instituto de Ciencia de Materiales (ICMUV), Universitat de València, P.O. Box 2085, 46071 Valencia, Spain; [email protected] 3 CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029 Madrid, Spain 4 Departamento de Farmacología, Universitat de València, Vicente Andrés Estellés S/n, Burjassot, 46100 Valencia, Spain * Correspondence: [email protected] (P.A.); [email protected] (A.M.C.) Abstract: A new hybrid organic–inorganic material for sensing spermine (Spm) and spermidine (Spd) has been prepared and characterized. The material is based on MCM-41 particles functionalized with an N-hydroxysuccinimide derivative and loaded with Rhodamine 6G. The cargo is kept inside the porous material due to the formation of a double layer of organic matter. The inner layer is covalently Citation: Barros, M.; López-Carrasco, bound to the silica particles, while the external layer is formed through hydrogen and hydrophobic A.; Amorós, P.; Gil, S.; Gaviña, P.; interactions. The limits of detection determined by fluorimetric titration are 27 µM and 45 µM for Parra, M.; El Haskouri, J.; Terencio, Spm and Spd, respectively. The sensor remains silent in the presence of other biologically important M.C.; Costero, A.M. Chromogenic amines and is able to detect Spm and Spd in both aqueous solution and cells. Chemodosimeter Based on Capped Silica Particles to Detect Spermine Keywords: detection; spermine; spermidine; silica particles and Spermidine. Nanomaterials 2021, 11, 818. https://doi.org/10.3390/ nano11030818 1. Introduction Academic Editor: Seung Uk Son Under normal physiological conditions, the concentration of polyamines in the body Received: 3 March 2021 is kept constant through a complex mechanism that involves biosynthetic, catabolic, and Accepted: 16 March 2021 transport processes [1–3]. An increase in intracellular polyamine concentration can be Published: 23 March 2021 correlated with uncontrolled cell proliferation and tumorigenic transformation [4–7]. Thus, high levels of polyamines have been related to skin, prostate, colon, or breast cancers [8–13]. Publisher’s Note: MDPI stays neutral Among the polyamines, spermidine (Spd) and spermine (Spm) (Figure1) have been proven with regard to jurisdictional claims in to be interesting biomarkers, in tissues and biological fluids, for detecting diverse patholog- published maps and institutional affil- ical situations. Hence, it has been demonstrated that low- and high-grade prostate cancer iations. tissues can be distinguished by the spermine concentrations among other metabolites [14]. Moreover, the concentrations of these amines in biological fluids have been used to detect other pathological conditions. For example, it has been demonstrated that the concentration of Spd + Spm in psoriasis patients is around 5.5-fold higher than in healthy individuals [15]. Copyright: © 2021 by the authors. By contrast, it has been also established that a low concentration of these amines can be Licensee MDPI, Basel, Switzerland. associated with aging related illnesses. In fact, the total Spd + Spm concentration in the This article is an open access article blood is lower in 60–80-year-old individuals than in 31–56-year-old individuals [16]. For distributed under the terms and this reason, these polyamines have been considered promising biomarkers for the early conditions of the Creative Commons detection of aging related illnesses, such as Parkinson’s disease [17]. Therefore, spermidine Attribution (CC BY) license (https:// seems to play an important role in memory and longevity [18]. For these reasons, the de- creativecommons.org/licenses/by/ tection of these polyamines is of great interest, and the design and synthesis of probes able 4.0/). Nanomaterials 2021, 11, 818. https://doi.org/10.3390/nano11030818 https://www.mdpi.com/journal/nanomaterials NanomaterialsNanomaterials2021 2021,,11 11,, 818 x FOR PEER REVIEW 22 of 1213 toand detect synthesis their presenceof probes in able biological to detect fluids, their such presence as urine, in biological and in tissues fluids, are such a constantly as urine, developingand in tissues field. are a constantly developing field. FigureFigure 1.1. StructureStructure ofof biologicalbiological polyamines.polyamines. InIn additionaddition toto thethe traditionaltraditional spectroscopicspectroscopic methodsmethods forfor detectingdetecting SpmSpm andand SpdSpd suchsuch asas MALDI–TOF MS MS [19], [19], GC-MS GC-MS [20], [20 or], Electr or Electrosprayospray Ionization Ionization and Time-Of-Flight and Time-Of-Flight Mass Mass[21], the [21 ],use the of use chromo- of chromo- or fluorogenic or fluorogenic probes probes is an is active an active research research field field due dueto the to thead- advantagesvantages of ofthese these types types of of sensors, sensors, such such as as no no need need of of expensive instrumental, real-timereal-time detectiondetection oror easy easy preparation preparation and and use. use. Some Some of theseof these probes probes are are based based on organic on organic molecules mole- thatcules experiment that experiment changes changes in fluorescence in fluorescence color after color reacting after reacting with the with polyamines the polyamines [22–24], whereas[22–24], whereas other protocols other protocols are based are on based the use on of the metallic use of metallic or organic or nanoparticlesorganic nanoparticles [25–27] (for[25–27] more (for details more see details Table see S1 Table in the S1 Supplementary in the supplementary Material). material). However, However, even though even mesoporous silica nanoparticles can also be used in the preparation of chromogenic or though mesoporous silica nanoparticles can also be used in the preparation of chromo- fluorogenic sensors [28], there is only one example in which this type of nanoparticles genic or fluorogenic sensors [28], there is only one example in which this type of nanopar- is used for detecting Spm and Spd [29] and, even in this case, the silica particles are ticles is used for detecting Spm and Spd [29] and, even in this case, the silica particles are decorated with Au that is responsible for the transduction mechanism. What is more, at decorated with Au that is responsible for the transduction mechanism. What is more, at the best of our knowledge, there are no examples of Spm or Spd detection using silica the best of our knowledge, there are no examples of Spm or Spd detection using silica nanoparticles capped with molecular gates. Silica mesoporous supports are often used as nanoparticles capped with molecular gates. Silica mesoporous supports are often used as containers because of their interesting properties: well-known chemistry, high inertness, containers because of their interesting properties: well-known chemistry, high inertness, easy functionalization, large surface, and specific volume, amongst others [30,31]. More easy functionalization, large surface, and specific volume, amongst others [30,31]. More specifically, the use of organic–inorganic hybrid materials has been demonstrated to offer specifically, the use of organic–inorganic hybrid materials has been demonstrated to offer many applications. Amid these materials, silica nanoparticles capped with molecular gatesmany have applications. shown to Amid be very these useful materials, not only silica in the nanoparticles delivery process capped but alsowith in molecular chemical detection.gates have Apart shown from to be the very inorganic useful scaffold not only these in the gated delivery nanodevices process contain, but also a in switchable chemical “gate-like”detection. Apart ensemble from capable the inorganic of being scaffold “opened” these or gated “closed” nanodevices when certain contain, external a switchable stimuli are“gate-like” applied. ensemble In this way, capable the silica of being scaffold “opened” works or as “closed” a container when in certain which external an appropriate stimuli dyeare applied. or fluorescent In this molecule way, the issilica loaded. scaffold The works molecular as a gatecontainer keeps in the which material an appropriate inside this containerdye or fluorescent until the adequatemolecule analyteis loaded. (that The works molecular as a specific gate keeps stimulus) the material “opens” inside the gate this allowingcontainer the until indicator the adequate (dye or analyte fluorophore) (that toworks be released as a specific and observed stimulus) in “opens” solution the [32 –gate34]. allowingBased the on indicator our experience (dye or in fluorophore) chemo-sensing to be [35 released–37] and and in the observed use of hybridin solution organic– [32– inorganic34]. nanomaterials functionalized with molecular gates for drug releasing and sens- ing [38Based–40], on we our herein experience report ain new chemo-sensing sensor able to[35–37]