Multifunctional Silica Nanoparticles Modified via Silylated-Decaborate Precursors

Abi-Ghaida, Fatima; Clément, Sébastien; Safa, Ali; Naoufal, Daoud; Mehdi, Ahmad

doi:https://doi.org/10.1155/2015/608432

Journal of Nanomaterials

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Abstract Introduction Results and Discussion Conclusion Acknowledgments Supplementary Materials References Copyright Related Articles

Research Article | Open Access

Volume 2015 | Article ID 608432 | https://doi.org/10.1155/2015/608432

Multifunctional Silica Nanoparticles Modified via Silylated-Decaborate Precursors

Fatima Abi-Ghaida,^1,2,3Sébastien Clément,¹Ali Safa,²Daoud Naoufal,^2,3and Ahmad Mehdi¹

Academic Editor: Yuebing Zheng

Received15 Aug 2015

Accepted08 Oct 2015

Published29 Oct 2015

Abstract

A new class of multifunctional silica nanoparticles carrying boron clusters (10-vertex closo-decaborate) and incorporating luminescent centers (fluorescein) has been developed as potential probes/carriers for potential application in boron neutron capture therapy (BNCT). These silica nanoparticles were charged in situ with silylated-fluorescein fluorophores via the Stöber method and their surface was further functionalized with decaborate-triethoxysilane precursors. The resulting decaborate dye-doped silica nanoparticles were characterized by TEM, solid state NMR, DLS, nitrogen sorption, elemental analysis, and fluorescence spectroscopy.

1. Introduction

Boron neutron capture therapy (BNCT) has been, for many decades, advocated as an innovative form of radiotherapy for diffuse tumors [1–4]. In BNCT, a nuclear reaction occurs when a low energy thermal neutron is absorbed by a nonradioactive boron-10 atom (20% of natural elemental boron). This reaction yields an unstable intermediate, ¹¹B, which immediately undergoes fission (~10⁻¹² sec) generating high linear energy transfer particles (⁷Li³⁺ and ⁴He²⁺) and low energy gamma (γ) rays [5, 6]. The advantage of this protocol over other therapeutic procedures lies in the small distance (~9-10 μm) traveled by the particles to dissipate their energy, which, thus, confines the damage to the tumor cells. Successful BNCT protocols highly depend on the sufficient and selective boron delivery to the targeted cells. Therefore, a preferential accumulation of boron-10 atoms in the desired location with effective concentrations (10–35 μg of boron atoms per g of tumor mass) is required [6]. Various boron carrier agents have been developed to this end including liposomes [7, 8], dendrimers [9], carbon nanotubes (CNTs) [10], boron nanotubes (BNTs) [11, 12], and magnetic nanoparticles [13, 14] but none have been fully integrated so far.

Although BNCT has demonstrated substantial results in several preclinical studies, this technique has not yet been fully accepted in the armory of tools for tumor treatment. Such delay could be attributed to the differences in the uptake and distribution of ¹⁰B among patients and to the uncertain determination of tumor-to-blood ¹⁰B concentration ratio. Consequently, the real time localization of the BNCT agents and estimation of the boron content inside tumors are required [1]. As such, entities that both contain as many boron atoms as possible (which could be triggered by neutron irradiation and are optically, magnetically, or radioactively active so as to indicate its exact location) and are able to obtain information in view of accumulated dose are highly desirable. Among the compounds developed for BNCT, momentous attention has been devoted to carboranes. Carboranes are icosahedral cages including carbon, boron, and hydrogen atoms [15–17]. The importance of these cages in BNCT is accentuated by their resistance to biodegradation and facile functionalization with lipophilic moieties in order to permit their specific and efficient delivery. Recently, several approaches have been developed for the synthesis of dual MRI (Magnetic Resonance Imaging)/BNCT agents containing carborane derivatives which allow their localization and the determination of ¹⁰B concentration ratio [18–21]. For example, Goswami et al. have recently described the synthesis of a polyfunctional MRI contrast agent based on single icosahedral-closo-dodecaborate cluster [B₁₂(OH)₁₂] carrying eleven Gd³⁺-DOTA chelates arms (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) [22]. A similar strategy has been also developed by Akimov et al. describing the coordination of gadolinium (III) salts by closo-decaborate-based polydentate ligands [23]. Unfortunately, such compounds encounter several drawbacks such as their presumed dissociation upon introduction into in vivo or in vitro systems and their limitations to MRI. To overcome such drawbacks, we propose to establish a covalent link between the decaborate cluster and the luminescent silica carrier agent through the grafting of silylated-decaborate derivatives on the surface of luminescent silica nanoparticles.

Silica-based nanoparticles (SNPs) are considered as viable candidates in theranostics applications (diagnostic and therapy protocols gathered into a single entity) [24–27]. Due to their morphological and structural versatility, their ease of synthesis, and their biocompatibility, these multifunctional systems have an escalating and synergistic alliance with the medicinal and pharmacological fields [28]. For instance, SNPs loaded with fluorophores are considered to be powerful tools for imaging [29] whereas mesoporous silica nanoparticles (MSNs) have dominated the field of drug carriers since their introduction [28]. Moreover, even though their possible toxicity (i.e., liberation of reactive oxygen species (ROS)) and biodegradability remain an issue of debate [30], these nanoparticles have shown numerous advantages over conventional therapy [31]. To date, more than two dozen multifunctional nanoparticle-based agents have been approved for clinical trials [32–34].

We have recently reported the synthesis of the first two members of the decaborate-silane precursor family by exploiting the amino [1-B₁₀H₉N₂]⁻ and carboxyl [2-B₁₀H₉CO]⁻anion derivatives. These silylated precursors were then immobilized on mesoporous SBA-15 silica in significant percentages [35]. Based on these results, we report herein the immobilization of decaborate-silane precursors through covalent grafting to silica (SiO₂) probe/carrier agent charged with silylated-FITC (fluorescein isothiocyanate) luminescent fluorophore. The implantation of a luminescent tracer in these decaborate-silica-based nanoparticles will allow obtaining crucial information on the pathway and the localization of these potential boron vehicles in future BNCT applications.

2. Experimental Section

2.1. Materials

All synthetic reactions were performed under an argon atmosphere using vacuum line and Schlenk techniques. All solvents were dried and distilled unless stated otherwise. (NH₄)₂[B₁₀H₁₀] was purchased from Katchem Ltd., Prague, and was dried under vacuum for 24 hours at 80°C prior to use. 3-Aminopropyltriethoxysilane (98%), N,N-diisopropylethylamine (99%), fluorescein isothiocyanate (98%), 3-isocyanatopropyltriethoxysilane (95%), oxalyl chloride (2.0 M in CH₂Cl₂), and tetraethyl orthosilicate (98%) were purchased from Sigma-Aldrich and used as received [36]. The silylated closo-decaborate clusters [PPh₄][1-B₁₀H₉NH₂CH₂CH₂NHCONH(CH₂)₃-Si(OC₂H₅)₃] (P1) and [PPh₄][(ⁱPr)₂(Et)NH][2-B₁₀H₉CONH(CH₂)₃-Si(OC₂H₅)₃] (P2) were synthesized as previously reported [30].

2.2. Characterization Methods

Elemental analyses were performed on a FLASH EA 1112 CHNS analyzer. Mass spectrometry was carried out on Synapt G2-S (Waters) equipped with an ESI source. The mass spectrum was recorded in the positive mode, between 100 and 1500 Da. The capillary voltage was 1000 V and the cone voltage was 30 V. The temperature sources and dissolution are, respectively, 120°C and 250°C. ¹¹B, ³¹P¹H}, and ²⁹Si¹H} NMR spectra in solution were recorded using an AMX 400 Bruker spectrometer operating, respectively, at 128 MHz, 162 MHz, and 80 MHz. Chemical shifts were externally calibrated to TMS in ²⁹Si, H₃PO₄ for ³¹P, and EtO₂·BF₃ for ¹¹B nucleus. Deuterated chloroform or acetonitrile was used as solvent. Transmission Electron Microscopy (TEM) observations were carried out at 100 kV on a JEOL 1200 EXII microscope. Solid state NMR spectra for ²⁹Si, ¹¹B, and ³¹P were recorded on a Varian VNMRS 300 solid spectrometer with a magnetic field strength of 7.05 T equipped with 7.5 mm MAS probe at 5 kHz as a spinning rate. Dynamic light scattering analysis was performed using a Cordouan Technologies DL 135 particle size analyzer instrument. Cumulant analysis of the correlation function was used to determine the mean hydrodynamic diameter (-average) and the polydispersity of each sample. UV-Visible spectra were recorded on a Jasco V-650 spectrophotometer in quartz cells. Fluorescence spectra were recorded at room temperature on an Edinburgh FS920 spectrophotometer. Emission and excitation spectra were corrected for the wavelength response of the system using correction factors supplied by the manufacturer.

2.3. Synthesis of N-(3-(Triethoxysilyl)propyl)-N-fluorescein-thioruea (Si-FITC)

Si-FITC was obtained according to a slightly modified literature procedure [37]. To a solution of fluorescein isothiocyanate (FITC) (150 mg, 0.385 mmol) in dry DMF (10 mL), 3-aminopropyltriethoxysilane (85 mg, 0.400 mmol) was added. The mixture was stirred for 4 h at room temperature under argon. The reaction progress was monitored by LCMS and ²⁹Si¹H} NMR. When the reaction was considered to be complete, the solvent was evaporated and the excess of 3-aminopropyltriethoxysilane was removed by washing with pentane. After drying under vacuum for 6 hours, 216 mg (92%) of Si-FITC was obtained as a bright yellow to orange solid. ²⁹Si¹H} (δ ppm, 79.5 MHz, DMSO-d6): −45 (s). ¹H NMR (δ ppm, 400 MHz, DMSO-d6): 0.51 (2H, t), 1.21 (9H, t), 1.56 (2H, m), 3.60 (2H, t), 3.91 (6H, q), 6.49–7.60 (9H, m), 10.01 (2H, s), 12.38 (1H, s). LCMS m/z calcd. for C₃₀H₃₄N₂O₈SSi [M+H]⁺: 611.19, found: 611.19. Anal. Calcd for C₃₀H₃₄N₂O₈SSi: C 59.00; H, 5.61; N, 4.59. Found: C 58.74; H 5.46, S 4.48.

2.3.1. Synthesis of Fluorescein-Doped Silica Nanoparticles (F_x@SiO₂Nps) ( = Mole Percentage of Si-FITC)

Silica nanoparticles were prepared according to the Stöber method [38]. To a water/absolute ethanol mixture (150 mL : 15 mL), ammonium hydroxide solution (25%) (3 mL) was added. When the stirred solution was stabilized at 30°C, TEOS (9 mL) and, simultaneously, varying amounts of the silylated FITC (Si-FITC) (0.05, 0.10, and 0.15% mole percent, resp.) in DMF (1 mL) were added. The mixture was vigorously stirred for 6 hours at room temperature. Then, the particle dispersion was centrifuged at 15°C (20000 r.p.m.). The resulting yellow solids were washed repeatedly by ethanol (10 mL), sonicated, and centrifuged again. Finally, the products were dried under vacuum at 60°C.

²⁹Si CP MAS-NMR: −94 ppm (Q²), −104 ppm (Q³), and −110 ppm (Q⁴).

Nitrogen sorption (adsorption branch) is as follows: F_0.05@SiO₂Nps - (m²/g): 56; (cm³/g): 0.09. F_0.10@SiO₂Nps - (m²/g): 59; (cm³/g): 0.11. F_0.15@SiO₂Nps - (m²/g): 61; (cm³/g): 0.12.

Elemental analyses are as follows: F_0.05@SiO₂Nps - Calcd (found): Si 45.59 (45.30), C 1.50 (1.81), N 0.15 (0.16). F_0.10@SiO₂Nps - Calcd (found): Si 44.45 (44.60), C 3.10 (3.53), N 0.30 (0.31). F_0.15@SiO₂Nps - Calcd (found): Si 43.18 (43.34), C 4.88 (4.90), N 0.47 (0.48).

2.3.2. Grafting of Silylated Borate Clusters (P1 and P2) (F_xPn@SiO₂Nps) ( = 0.05, 0.10, and 0.15%, )

The silylated closo-decaborate clusters P1 and P2 (Scheme 2) were used to modify surface of the silica nanoparticles. To a dispersion of F_x@SiO₂Nps (500 mg) in acetonitrile (15 mL), 250 mg of P1 and P2 was added. The mixtures were refluxed overnight. After cooling, the particle dispersions were centrifuged at 15°C (20000 r.p.m.). The resulting solids were repeatedly washed with acetonitrile and diethyl ether and centrifuged. The products were finally dried under vacuum at 60°C and denoted as F_xP1@SiO₂Nps and F_xP2@SiO₂Nps.

¹¹B CP-MAS NMR: F_xP1@SiO₂Nps (8.9 (B₁), −1.8 (B₁₀), −10 to −37 () ppm), F_xP2@SiO₂Nps (−0.5 (B_1,10), −18 to −35 () ppm). ²⁹Si CP-MAS NMR: −56 ppm (T²), −69 ppm (T³), −94 ppm (Q²), −105 ppm (Q³) and −111 ppm (Q⁴). ³¹P CP-MAS NMR: 23 ppm.

Surface areas and pore volumes determined from nitrogen adsorption branch are as follows: F_0.05P1@SiO₂Nps - (m²/g): 57; (cm³/g): 0.10. F_0.10P1@SiO₂Nps - (m²/g): 62; (cm³/g): 0.12. F_0.15P1@SiO₂Nps - (m²/g): 64; (cm³/g): 0.12. F_0.05@SiO₂Nps - (m²/g): 58; (cm³/g): 0.10. F_0.10@SiO₂Nps - (m²/g): 61; (cm³/g): 0.11. F_0.15@SiO₂Nps - (m²/g): 63; (cm³/g): 0.12.

Elemental analyses are as follows: F_0.05P1@SiO₂Nps - Calcd (found): Si 37.91 (37.30), B 3.07 (3.10), C 11.48 (11.81), N 1.32 (1.29). F_0.10P1@SiO₂Nps - Calcd (found): Si 31.64 (31.83), B 5.24 (5.21), C 19.70 (19.57), N 2.25 (2.34). F_0.15P1@SiO₂Nps - Calcd (found): Si 27.03 (27.51), B 6.79 (6.48), C 25.70 (25.90), N 2.93 (2.91). F_0.05P2@SiO₂Nps - Calcd (found): Si 34.44 (34.80), B 3.98 (4.00), C 16.63 (16.90), N 1.14 (1.18). F_0.10P2@SiO₂Nps - Calcd (found): Si 25.90 (25.41), B 6.79 (7.01), C 28.99 (28.49), N 1.93 (1.89). F_0.15P2@SiO₂Nps - Calcd (found): Si 21.46 (22.10), B 8.19 (8.34), C 35.20 (35.97), N 2.36 (2.71).

3. Results and Discussion

Prior to the preparation of luminescent silica nanoparticles (F_x@SiO₂Nps), the silylated fluorophore (Si-FITC) was synthesized by the reaction of fluorescein isothiocyanate (FITC) with 3-aminopropyltriethoxysilane (APTES) in dry DMF at room temperature (Scheme 1). The conversion of FITC into the corresponding silylated compound was followed by NMR spectroscopy (ESI, see Figure S1 in Supplementary Material available online at http://dx.doi.org/10.1155/2015/608432) and LCMS. A complete conversion of FITC was achieved in 4 h.

The synthesis of the dye-doped silica particles was performed using a modified Stöber method (Sol-gel process) where tetraethoxysilane (TEOS) and Si-FITC (0.05, 0.10, and 0.15% per mole) were hydrolyzed in the presence of ethanol/water/ammonium hydroxide mixture and maintained for six hours at room temperature under stirring (Scheme 2).

The resulting mixtures were centrifuged and washed repeatedly by ethanol and acetonitrile to yield quantitatively yellow dye-doped silica nanoparticles. The repetitive washing cycles allow the removal of low weight oligomers, adsorbed and unreacted species. The concentration of TEOS to ethanol and water was kept moderate, thus permitting the aggregation of primary particles into a single uniform size with sufficient surface area (or diameter) adequate for postsynthesis surface modification (grafting).

The resulting dye-doped SNPs (F_x@SiO₂NPs) were analyzed by nitrogen sorption (ESI, Figure S2). A relatively small surface area ( = 56–61 m²/g) and an insignificant pore volume ( = 0.09–0.11 cm³/g) were obtained indicating a nonporous silica matrix. TEM analysis revealed that the mean particle size of dye-doped SNPs F_x@SiO₂Nps (, 0.10, and 0.15) is between 225 nm and 258 nm. As an example, the TEM images of F_0.10@SiNps are shown in Figure 1 confirming that uniform and monodispersed particles are obtained. These results were then confirmed by dynamic light scattering (DLS) analysis where the average diameters of the different batch sized particles were found to be between 257 and 372 nm with a polydispersity index (PI) of 0.05 to 0.15 which implies relative uniformity. The size of these particles, as estimated from the TEM data, is smaller than the size found by DLS since, in DLS, the hydrodynamic radius of the particles is measured (Table 1). The ²⁹Si CP-MAS NMR spectra of FITC-doped SNPs exhibit the siloxane peaks Q², Q³, and Q⁴ at −94, −104, and −110 ppm, respectively (ESI, Figure S3).

Finally, the two silylated closo-decaborate clusters P1 and P2 were grafted onto the surface of the Si-FITC-doped NPs F_x@SiO₂Nps leading to decaborate-surface-modified NPs F_xP1@SiO₂Nps (modified with P1) and F_xP2@SiO₂Nps (modified with P2) (Figure 2).

(a)

(b)

(c)

(d)

The hydrodynamic radius of the decaborate-surface-modified silica nanoparticles was measured by DLS analysis in EtOH and was found to be in the range 350–450 nm with a polydispersity index (PI) between 0.05 and 0.15 (ESI, Figure S4). This underlines the uniform distribution of the particle diameter as observed by TEM (Table 1). The increase in the hydrodynamic diameter after grafting precursors P1 and P2 indicates covalent coupling of the triethoxysilylated precursors P1 and P2 to the hydroxyl group present on the SiO₂Nps surface.

²⁹Si, ³¹P, and ¹¹B solid state CP-MAS NMR spectra were recorded for all surface-modified nanoparticles. Solid state ¹¹B CP-MAS NMR spectra of the decaborate-functionalized luminescent silica nanoparticles F_xP1@SiO₂Nps and F_xP2@SiO₂Nps are quite consistent with the ¹¹B NMR spectra of P1 and P2 in solution (Figure 3). These results further confirm the presence of the silylated-decaborate clusters on the surface of the nanoparticles. For instance, ¹¹B CP-MAS NMR spectrum of F_0.15P1@SiO₂Nps reveals the presence of three distinct peaks: a peak at ~8 ppm (versus 7.5 ppm in liquid NMR) corresponding to the substituted B₁ atom at an apical position, another peak at ~−1.8 ppm (versus −1.2 ppm in liquid NMR) for B₁₀ atom position, and a broad peak between −10 and −37 ppm for the remaining eight equatorial B atoms (versus −27 to −32 ppm in liquid NMR). In contrast, two peaks at ~−0.5 ppm (corresponding to B_1,10) and between −18 and −35 ppm (B₂ is overlapped with the remaining ) are observed for F_0.15P2@SiO₂Nps.

(a)

(b)

The ²⁹Si CP-MAS solid state NMR spectra of F_0.15P1@SiO₂Nps and F_0.15P2@SiO₂Nps give information on the different silicon environment present, where siloxane peaks Q², Q³, and Q⁴ are observed at −94, −105, and −111 ppm, respectively. However, rather small but distinguished peaks corresponding to T² and T³ environment can be observed at −56 and −69 ppm (ESI, Figure S5). This is generally attributed to the low percentage of grafted precursors on the surface of the silica nanoparticles. The ³¹P CP-MAS NMR spectra of F_0.15P1@SiO₂Nps and F_0.15P2@SiO₂Nps exhibit a singlet at ~23 ppm relevant to the presence of the countercation.

The percentage of incorporated boron atoms was determined from Elemental Analyses (Table 2). The data disclosed a moderate anchoring of the precursors where a maximum value of 1.0% (corresponding to 10% of boron atoms) was attained. It is interesting to note that the anchoring rate for P2 exceeds that of P1 due to the steric hindrance and longer chain for P1.

The optical properties of the Si-FITC-doped particles (F_x@SiO₂Nps) were studied before and after surface modification with decaborate. FITC was chosen since it is a suitable and well-known fluorescent probe for biological studies [39–41]. Indeed, FITC absorbs and emits the visible region of the spectrum, respectively, at 490 nm and 520 nm. The optical properties of fluorescein are inherent to the presence of the xanthene and benzoic acid moieties, which can exist in multiple ionization states [42]. Despite its widespread use in bioassays, this organic dye has well-known deficiencies, such as low resistance to photodegradation, decreased fluorescence intensity upon conjugation with biomolecules, and pH dependent fluorescence properties. The incorporation of Si-FITC into silica matrices has been known to effectively circumvent these issues by improving its photostability and preventing the decrease in fluorescence intensity.

The absorption and emission spectra of the prepared Si-FITC-doped silica nanoparticles are shown in Figure 4. An absorption band at nm is noticed in the absorption spectra of F_x@SiO₂Nps which corresponds to the fluorescein absorption. The emission spectrum of the F_x@SiO₂Nps exhibits an emission band centered at 520 nm where intensity increases with the Si-FITC content in the silica matrix. It is interesting to note that the modification of the SNPs with closo-decaborate does not significantly modify the absorption and emission spectra, thus maintaining the inherent luminescent properties of the F_x@SiO₂Nps (ESI, Figure S6).

(a)

(b)

4. Conclusion

A new class of decaborate-surface-modified luminescent SNPs has been developed for potential applications in boron neutron capture therapy. To this aim, different percentages (2–10% of boron atoms) of silylated-decaborate clusters (P1 and P2) were grafted at the surface of SNPs incorporating a fluorescein-based fluorophore in 0.05, 0.10, and 0.15% per mole, respectively. The covalent grafting of the closo-decaborate cluster onto the dye-doped SNPs does not alter the photoluminescence properties of the prepared nanoparticles. These decaborate-modified/luminescent silica nanoparticles could be promising prototypes for future BNCT applications allowing the precise localization of these potential boron vehicles. However, improvements have to be considered since only a low content of P1 and P2 was grafted. To increase the content of boron in silica nanoparticles, we propose the cocondensation of TEOS and decaborate-triethoxysilane to produce boron-enriched SiO₂ core in addition to surface-modification. Such a modification requires the design and synthesis of bisilylated-decaborate silane precursors which are currently under investigation. Additional research will also be carried out to further increase the solubility of the decaborate-silica nanoparticles in biological media by PEG functionalization for future testing in BNCT.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Acknowledgments

The authors thank the CNRS, the University of Montpellier, and the Conseil National de la Recherche Scientifique of Lebanon (CNRSL) (http://www.cnrs.edu.lb/) for financial support.

Supplementary Materials

Additional data and experimental conditions and procedures can be found in the electronic supporting information. The data includes the ²⁹Si NMR of Si-FITC, the Nitrogen sorption (BET) isotherms of F_x@SiO₂NPs, the dynamic light scattering and ²⁹Si CP-MAS NMR spectra of F_0.10P1@SiO₂NPs and the absorption and emission spectra of decaborate dye-doped silica nanoparticles.

Supplementary Material

References

S. Chandra, T. Ahmad, R. F. Barth, and G. W. Kabalka, “Quantitative evaluation of boron neutron capture therapy (BNCT) drugs for boron delivery and retention at subcellular-scale resolution in human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS),” Journal of Microscopy, vol. 254, no. 3, pp. 146–156, 2014.
View at: Publisher Site | Google Scholar
R. L. Raymond, “Critical review, with an optimistic outlook, on Boron Neutron Capture Therapy (BNCT),” Applied Radiation and Isotopes, vol. 88, pp. 2–11, 2014.
View at: Publisher Site | Google Scholar
N. S. Hosmane, Ed., Boron Science: New Technologies and Applications, CRC Press, 2012.
Y. Zhu, K. C. Yan, J. A. Maguire, and N. S. Hosmane, “Boron-based hybrid nanostructures: novel applications of modern materials,” in Hybrid Nanomaterials: Synthesis, Characterization and Applications, B. P. S. Chauhan, Ed., pp. 181–198, John Wiley & Sons, Hoboken, NJ, USA, 2011.
View at: Google Scholar
Z. Yinghuai, K. C. Yan, J. A. Maguire, and N. S. Hosmane, “Recent developments in boron neutron capture therapy (BNCT) driven by nanotechnology,” Current Chemical Biology, vol. 1, no. 2, pp. 141–149, 2007.
View at: Publisher Site | Google Scholar
A. H. Soloway, W. Tjarks, B. A. Barnum et al., “The chemistry of neutron capture therapy,” Chemical Reviews, vol. 98, no. 4, pp. 1515–1562, 1998.
View at: Publisher Site | Google Scholar
S. Tachikawa, T. Miyoshi, H. Koganei et al., “Spermidinium closo-dodecaborate-encapsulating liposomes as efficient boron delivery vehicles for neutron capture therapy,” Chemical Communications, vol. 50, no. 82, pp. 12325–12328, 2014.
View at: Publisher Site | Google Scholar
D. A. Feakes, K. Shelly, C. B. Knobler, and M. F. Hawthorne, “Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 8, pp. 3029–3033, 1994.
View at: Publisher Site | Google Scholar
M. V. Backer, T. I. Gaynutdinov, V. Patel et al., “Vascular endothelial growth factor selectively targets boronated dendrimers to tumor vasculature,” Molecular Cancer Therapeutics, vol. 4, no. 9, pp. 1423–1429, 2005.
View at: Publisher Site | Google Scholar
Y. H. Zhu, T. P. Ang, K. Carpenter, J. A. Maguire, N. S. Hosmane, and M. Takagaki, “Substituted carborane-appended water-soluble single-wall carbon nanotubes: new approach to boron neutron capture therapy drug delivery,” Journal of the American Chemical Society, vol. 127, no. 27, pp. 9875–9880, 2005.
View at: Publisher Site | Google Scholar
T. T. Xu, J.-G. Zheng, N. Wu et al., “Crystalline boron nanoribbons: synthesis and characterization,” Nano Letters, vol. 4, no. 5, pp. 963–968, 2004.
View at: Publisher Site | Google Scholar
D. Ciuparu, R. F. Klie, Y. Zhu, and L. Pfefferle, “Synthesis of pure boron single-wall nanotubes,” The Journal of Physical Chemistry B, vol. 108, no. 13, pp. 3967–3969, 2004.
View at: Publisher Site | Google Scholar
Y. Zhu, Y. Lin, Y. Z. Zhu, J. Lu, J. A. Maguire, and N. S. Hosmane, “Boron drug delivery via encapsulated magnetic nanocomposites: a new approach for BNCT in cancer treatment,” Journal of Nanomaterials, vol. 2010, Article ID 409320, 8 pages, 2010.
View at: Publisher Site | Google Scholar
C. Alexiou, W. Arnold, R. J. Klein et al., “Locoregional cancer treatment with magnetic drug targeting,” Cancer Research, vol. 60, no. 23, pp. 6641–6648, 2000.
View at: Google Scholar
M. Scholz and E. Hey-Hawkins, “Carbaboranes as pharmacophores: properties, synthesis, and application strategies,” Chemical Reviews, vol. 111, no. 11, pp. 7035–7062, 2011.
View at: Publisher Site | Google Scholar
I. Viñas and C. Teixidor, “The uniqueness of boron as a novel challenging element for drugs in pharmacology, medicine and for smart biomaterials,” Future Medicinal Chemistry, vol. 5, no. 6, pp. 617–619, 2013.
View at: Publisher Site | Google Scholar
J. F. Valliant, K. J. Guenther, A. S. King et al., “The medicinal chemistry of carboranes,” Coordination Chemistry Reviews, vol. 232, no. 1-2, pp. 173–230, 2002.
View at: Publisher Site | Google Scholar
D. Alberti, A. Toppino, S. Geninatti Crich et al., “Synthesis of a carborane-containing cholesterol derivative and evaluation as a potential dual agent for MRI/BNCT applications,” Organic and Biomolecular Chemistry, vol. 12, no. 15, pp. 2457–2467, 2014.
View at: Publisher Site | Google Scholar
G. Chen, J. Yang, G. Lu et al., “One stone kills three birds: novel boron-containing vesicles for potential BNCT, controlled drug release, and diagnostic imaging,” Molecular Pharmaceutics, vol. 11, no. 10, pp. 3291–3299, 2014.
View at: Publisher Site | Google Scholar
C.-H. Lai, N.-C. Lai, Y.-J. Chuang, F.-I. Chou, C.-M. Yang, and C.-C. Lin, “Trivalent galactosyl-functionalized mesoporous silica nanoparticles as a target-specific delivery system for boron neutron capture therapy,” Nanoscale, vol. 5, no. 19, pp. 9412–9418, 2013.
View at: Publisher Site | Google Scholar
A. Toppino, M. E. Bova, S. G. Crich et al., “A carborane‐derivative ‘click’ reaction under heterogeneous conditions for the synthesis of a promising lipophilic MRI/GdBNCT agent,” Chemistry, vol. 19, no. 2, pp. 721–728, 2013.
View at: Publisher Site | Google Scholar
L. N. Goswami, L. Ma, S. Chakravarty, Q. Cai, S. S. Jalisatgi, and M. F. Hawthorne, “Discrete nanomolecular polyhedral borane scaffold supporting multiple gadolinium(III) complexes as a high performance MRI contrast agent,” Inorganic Chemistry, vol. 52, no. 4, pp. 1694–1700, 2013.
View at: Publisher Site | Google Scholar
S. S. Akimov, E. Y. Matveev, A. S. Kubasov, G. A. Razgonyaeva, K. Y. Zhizhin, and N. T. Kuznetsov, “Polydentate ligands based on closo-decaborate anion for the synthesis of gadolinium(III) complexes,” Russian Chemical Bulletin, vol. 62, no. 6, pp. 1417–1421, 2013.
View at: Publisher Site | Google Scholar
J. Croissant, A. Chaix, O. Mongin et al., “Two-photon-triggered drug delivery via fluorescent nanovalves,” Small, vol. 10, no. 9, pp. 1752–1755, 2014.
View at: Publisher Site | Google Scholar
N. T. Chen, S. H. Cheng, J. S. Souris, C. T. Chen, C. Y. Moub, and L. W. Lo, “Theranostic applications of mesoporous silica nanoparticles and their organic/inorganic hybrids,” Journal of Materials Chemistry B, vol. 1, no. 25, pp. 3128–3135, 2013.
View at: Publisher Site | Google Scholar
Z. Li, J. C. Barnes, A. Bosoy, J. F. Stoddart, and J. I. Zink, “Mesoporous silica nanoparticles in biomedical applications,” Chemical Society Reviews, vol. 41, no. 7, pp. 2590–2605, 2012.
View at: Publisher Site | Google Scholar
M. W. Ambrogio, C. R. Thomas, Y.-L. Zhao, J. I. Zink, and J. F. Stoddart, “Mechanized silica nanoparticles: a new frontier in theranostic nanomedicine,” Accounts of Chemical Research, vol. 44, no. 10, pp. 903–913, 2011.
View at: Publisher Site | Google Scholar
K. E. Sapsford, W. R. Algar, L. Berti et al., “Functionalizing nanoparticles with biological molecules: developing chemistries that facilitate nanotechnology,” Chemical Reviews, vol. 113, no. 3, pp. 1904–2074, 2013.
View at: Publisher Site | Google Scholar
E. Mahon, D. R. Hristov, and K. A. Dawson, “Stabilising fluorescent silica nanoparticles against dissolution effects for biological studies,” Chemical Communications, vol. 48, no. 64, pp. 7970–7972, 2012.
View at: Publisher Site | Google Scholar
S. J. Soenen, B. Manshian, S. H. Doak, S. C. De Smedt, and K. Braeckmans, “Fluorescent non-porous silica nanoparticles for long-term cell monitoring: cytotoxicity and particle functionality,” Acta Biomaterialia, vol. 9, no. 11, pp. 9183–9193, 2013.
View at: Publisher Site | Google Scholar
M. Helle, E. Rampazzo, M. Monchanin et al., “Surface chemistry architecture of silica nanoparticles determine the efficiency of in Vivo fluorescence lymph node mapping,” ACS Nano, vol. 7, no. 10, pp. 8645–8657, 2013.
View at: Publisher Site | Google Scholar
S. Iltis, J. Choi, M. Vollmers, M. Shenoi, J. Bischof, and G. J. Metzger, “In vivo detection of the effects of preconditioning on LNCaP tumors by a TNF-α nanoparticle construct using MRI,” NMR in Biomedicine, vol. 27, no. 9, pp. 1063–1069, 2014.
View at: Publisher Site | Google Scholar
J. O'Shaughnessy, W. J. Gradishar, P. Bhar, and J. Iglesias, “Nab-paclitaxel for first-line treatment of patients with metastatic breast cancer and poor prognostic factors: a retrospective analysis,” Breast Cancer Research and Treatment, vol. 138, no. 3, pp. 829–837, 2013.
View at: Publisher Site | Google Scholar
J. Choi, A. A. Burns, R. M. Williams et al., “Core-shell silica nanoparticles as fluorescent labels for nanomedicine,” Journal of Biomedical Optics, vol. 12, no. 6, Article ID 064007, 11 pages, 2007.
View at: Publisher Site | Google Scholar
F. Abi-Ghaida, Z. Laila, G. Ibrahim, D. Naoufal, and A. Mehdi, “New triethoxysilylated 10-vertex closo-decaborate clusters. Synthesis and controlled immobilization into mesoporous silica,” Dalton Transactions, vol. 43, no. 34, pp. 13087–13095, 2014.
View at: Publisher Site | Google Scholar
International Standard, “Particle size analysis—dynamic light scattering,” ISO 22412, International Organization for Standardization (ISO), 2008.
View at: Google Scholar
B.-S. Bae and S.-Y. Kwak, US Patent Application Publication 20120153229 A1 20120621, 2012.
W. Stöber, A. Fink, and E. Bohn, “Controlled growth of monodisperse silica spheres in the micron size range,” Journal of Colloid And Interface Science, vol. 26, no. 1, pp. 62–69, 1968.
View at: Publisher Site | Google Scholar
A. Schulz and C. McDonagh, “Intracellular sensing and cell diagnostics using fluorescent silica nanoparticles,” Soft Matter, vol. 8, no. 9, pp. 2579–2585, 2012.
View at: Publisher Site | Google Scholar
A. Burns, H. Ow, and U. Wiesner, “Fluorescent core-shell silica nanoparticles: towards ‘Lab on a Particle’ architectures for nanobiotechnology,” Chemical Society Reviews, vol. 35, no. 11, pp. 1028–1042, 2006.
View at: Publisher Site | Google Scholar
H. Ow, D. R. Larson, M. Srivastava, B. A. Baird, W. W. Webb, and U. Wiesnert, “Bright and stable core-shell fluorescent silica nanoparticles,” Nano Letters, vol. 5, no. 1, pp. 113–117, 2005.
View at: Publisher Site | Google Scholar
A. Imhof, M. Megens, J. J. Engelberts, D. T. N. De Lang, R. Sprik, and W. L. Vos, “Spectroscopy of fluorescein (FITC) dyed colloidal silica spheres,” The Journal of Physical Chemistry B, vol. 103, no. 9, pp. 1408–1415, 1999.
View at: Publisher Site | Google Scholar

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Copyright © 2015 Fatima Abi-Ghaida et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Journal of Nanomaterials

Multifunctional Silica Nanoparticles Modified via Silylated-Decaborate Precursors

Abstract

1. Introduction

2. Experimental Section

2.1. Materials

2.2. Characterization Methods

2.3. Synthesis of N-(3-(Triethoxysilyl)propyl)-N-fluorescein-thioruea (Si-FITC)

2.3.1. Synthesis of Fluorescein-Doped Silica Nanoparticles (Fx@SiO2Nps) ( = Mole Percentage of Si-FITC)

2.3.2. Grafting of Silylated Borate Clusters (P1 and P2) (FxPn@SiO2Nps) ( = 0.05, 0.10, and 0.15%, )

3. Results and Discussion

4. Conclusion

Conflict of Interests

Acknowledgments

Supplementary Materials

References

Copyright

2.3.1. Synthesis of Fluorescein-Doped Silica Nanoparticles (F_x@SiO₂Nps) ( = Mole Percentage of Si-FITC)

2.3.2. Grafting of Silylated Borate Clusters (P1 and P2) (F_xPn@SiO₂Nps) ( = 0.05, 0.10, and 0.15%, )