A Facile Strategy for In Situ Core-Template-Functionalizing Siliceous Hollow Nanospheres for Guest Species Entrapment
© to the authors 2009
Received: 9 February 2009
Accepted: 15 June 2009
Published: 27 June 2009
The shell wall-functionalized siliceous hollow nanospheres (SHNs) with functional molecules represent an important class of nanocarriers for a rich range of potential applications. Herein, a self-templated approach has been developed for the synthesis of in situ functionalized SHNs, in which the biocompatible long-chain polycarboxylates (i.e., polyacrylate, polyaspartate, gelatin) provide the framework for silica precursor deposition by simply controlling chain conformation with divalent metal ions (i.e., Ca2+, Sr2+), without the intervention of any external templates. Metal ions play crucial roles in the formation of organic vesicle templates by modulating the long chains of polymers and preventing them from separation by washing process. We also show that, by in situ functionalizing the shell wall of SHNs, it is capable of entrapping nearly an eightfold quantity of vitamin Bc in comparison to the bare bulk silica nanospheres. These results confirm the feasibility of guest species entrapment in the functionalized shell wall, and SHNs are effective carriers of guest (bio-)molecules potentially for a variety of biomedical applications. By rationally choosing the functional (self-templating) molecules, this concept may represent a general strategy for the production of functionalized silica hollow structures.
Inorganic hollow or porous micro-/nanostructures are of great interest in many current and emerging areas of technology partly because of their hollow or porous chamber, high specific surface area, low toxicity and low effective density [1–4]. Such hollow or porous capsules can pave the way for industrial, environmental, biomedical and biotechnological applications such as catalysis, separation, delivery, immobilization and so on [5–8]. Recently, the number of biologically active proteins, drugs and antimicrobials used to treat/prevent disease is growing rapidly, but appropriate inorganic carriers for introduction of these therapeutics into body are often lacking [9–11]. Silica nanoparticles (i.e., bulk, hollow and porous structure) are nontoxic, bioresorbable matrix as versatile carriers and polishing component of toothpastes primarily due to the fine thermal stability and chemical inertia [12–18]. In particular, biomedical and biotechnological applications with siliceous hollow nanospheres (SHNs) are currently focused on guest (bio-)molecules delivery and controlled release. Basically, these applications require the functionalized shell wall with biocompatible functional molecules to effectively improve the loading density of guest species, which would also endow them with diverse properties. Among the various hollow particles production techniques, the template route has been investigated most extensively due to its flexibility in controlling the particles size from micrometer- to nanometer scales [19, 20]. Although the classical sol–gel processes result in SHNs by using the core-template of micelles and rigid particles [12, 19–21], the synthetic procedures are multistep and complex, and the SHNs have significant shortcomings that limit their functionality in the silica shell as sacrificing templates by either calcination or chemical dissolution. So far, several efforts have been directed toward the structural organization of organic–inorganic hybrid SHNs via the catalytic activity of polymers or vesicle template, but they suffer from potential biocompatibility and ill-defined morphology problems [22–25]. Thus, it is highly desired to develop facile synthesis pathway for SHNs formation with shell wall functionalization for biomedical applications.
The DNA conformational changes, such as nanoscale toroid, spheroid and rodlike structure, modulated by multivalent cations (MVCs) have been widely appreciated as superb model system for understanding gene packing in biological systems [26–28]. This process prompts a number of analogous studies on coils conformation and inorganic superstructure formation by templating of ions-initiating semiflexible polyelectrolyte polymers [29–34]. Particularly, recent studies of DNA template synthesis have also revealed that the ‘cationic’ plasmid DNA form can act as an attractive template for the formation of ordered circular and rodlike silica nanostructures . We hypothesize that the metal ions (for example, alkaline earth metals) are able to crosslink long-chain polyanionic molecules to form specific morphology with more complexity in comparison with DNA toroid. Thus, a new strategy for constructing a spherical complex (for example, vesicle) using a wide range of polymers for templating SHNs formation has been awaited.
On the basis of these considerations, we have developed a one-step synthesis of biologically friendly SHNs with functionalized hollow chamber from polymers self-templated pathway, thanks only to electrostatic interaction between polycarboxylates and divalent metal ions. The SHNs are synthesized by a sonochemically assisted wet chemical reaction, and metal ions are used as polymer conformation modulators, without the intervention of any external templates and potentially toxic surfactants or mediums. Specifically, polyacrylate, polyaspartate and alkaline-processed gelatin molecules containing COO− groups are initially selected because of their biocompatible and noninflammatory nature, and especially because of their reversible conformation changes with small external pH changes [33, 36, 37]. To our knowledge, this is the first report on the mild synthesis of hollow spheres composed of silica shell wall, which is simultaneously (in situ) functionalized by templating biocompatible polymers under the modulation of biologically essential metal ions in aqueous medium.
Materials and Reagents
All chemicals used were commercially available. Reagents used for the synthesis of hollow silica nanospheres included tetraethoxysilane (TEOS), absolute ethanol (99.7%), calcium nitrate (Ca(NO3)2·4H2O, 99.5%), strontium nitrate (Sr(NO3)2·4H2O, 99.5%), aqueous ammonia (28 wt%) were purchased from Shanghai Chemical Reagent Co. (SCRC, China) and used as received. The polyacrylate sodium (30 wt%, averageMw~2.5 KDa) (abbreviated as PAS2.5) and poly(aspartic acid) (30 wt%, averageMw~5.0 KDa) (abbreviated as PAsp5), gelatin (alkalic-processing; 10 wt%, averageMw~75 KDa) were obtained from SCRC. Deionized distilled water (DDW) was used throughout the experiment.
Synthesis of Siliceous Hollow Nanospheres
Synthesis details and conditions for the preparation of silica nanospheres
Divalent metal ion
Ageing time (min)
Ca or Sr
5, 12, 20
Ca or Sr
Hollow and bulk
Ca or Sr
Ca or Sr
Examination of the As-Synthesized SHNs as a Carrier of Biomolecules
The 0.8 wt% Vitamin Bc (denoted as VB, KCl solution, pH = 10.5) and the freshly as-synthesized SHNs were mixed in a suspension with the weight ratio of VB/SHNs = 1/2, which was stirred vigorously for 8 h. After rinsed with KCl solution (pH = 10.5) to remove the unentrapped molecules, the powders with the entrapped VB dried in vacuum. As a comparison of the test on entrapment efficiency, the experiment of bare bulk silica nanospheres (100 nm or less in diamater) entrapping VB was taken as control.
The dried powders were determined by X-ray diffraction (XRD, Rigaku D/max-rA) with Cu Kα radiation at a scanning rate of 0.01°/min and Fourier transform Infrared (FTIR, Nicolet) for the phase composition. The morphology and chemical composition of the particles were determined by transmission electron microscopy (TEM, JEOL JEM-2010) connected with energy-dispersive X-ray analysis (EDX, INCA EDAX, element > B) operating at 200 kV. The scanning electric microscopy (SEM) images were taken on a JEOL JEM-6700F microscope. Samples were deposited onto quartz slides. Thermo-gravimteric analysis (TGA) was performed using a TG/DTA6200, with heating rate of 10 °C min−1in air. All the samples were washed with DDW and dried to remove the physicosorbed polymers prior to analysis.
Results and Discussion
More recently, other authors have also reported that block copolymer micelle initialized in chloroform, besides the cationic DNA circular or coiled-coil structures , can act as morphologically changeable templates for hollow silica spheres or tubules formation . Indeed, we agree when these aggregated polymer micelle is viewed as template for SHNs, in which the terminal amide groups instead of the cationized side groups is the anchor point for silica nucleation. In the present study, we find significant differentiation from the polymer templates in the presence and absence of metal ions, however (for example, those shown in Table.1, No. 1 and No. 3). This phenomenon is evidently deviated from the existing aggregated polymer-templating synthesis with and without the assistance of sonication [14, 15].
In addition, our many check and reproducible experiments, for example the “cationic” polyepoxysuccinate vesicles, validated the SHNs production while the other reaction conditions remained the same (data not shown). It is obvious that the side-chain complexity of polyacrylate, polyaspartate and gelatin is increased progressively. The alkalic-processed gelatin, formed from denatured and degraded collagen, has a poorly defined structure, but the portions of collagen molecules with characteristic triple helical structure are still present and lie in parallel layers. Thus, this molecule possesses a great proportion of carboxyl groups, rending it negatively charged and expanding in the alkaline aqueous solution.
In summary, we have developed a more facile and versatile method to obtain highly functionalized HSNs with openings. The shell wall thickness of the hollow spheres can be easily tailored by varying the aging time, and the particle size can be controlled below submicron dimension. This method is based on the in situ adsorption of functional molecules in the hollow chamber of hollow spheres in an aqueous medium, without involving additional template and hazardous additives. The participation of electrostatic interactions between a diversity of carboxylic groups-rich long-chain polymers and divalent metal ions was evidenced. Extension of the present versatile technique to other functional polymers may enable the preparation of siliceous hollow carriers with different functionalities. These materials with high functionalized shell wall could be good candidates for guest molecules adsorption, which is particularly useful in the biomolecules delivery for therapy and antimicrobial agent release for preventing caries.
The authors would like to acknowledge financial support by the FSTDZP (2008C21058), CFZUWST (H20080039) and ZCNI (J30802).
- D.L. Wilcox, M. Berg, T. Bernat, D. Kellerman, J.K. Cochran (Eds.), Hollow and Solid Spheres ans Microspheres. MRS symposium Proceedings. Vol. 372 Materials Research Society, Pittsburg, PA, 1995Google Scholar
- Perkin KK, Tuner JL, Wooley KL, Mann S: Nano. Lett.. 2005, 5: 1457. COI number [1:CAS:528:DC%2BD2MXltlGntro%3D]; Bibcode number [2005NanoL...5.1457P] 10.1021/nl050817wView ArticleGoogle Scholar
- Cai Y, Pan H, Xu X, Hu Q, Li L, Tang R: Chem. Mater.. 2006, 19: 3081. 10.1021/cm070298tView ArticleGoogle Scholar
- Collins AM, Spickermann C, Mann S: J. Chem. Mater.. 2003, 13: 1112. COI number [1:CAS:528:DC%2BD3sXjtVCntbo%3D] 10.1039/b301183fView ArticleGoogle Scholar
- Lal M, Levy L, Kim KS, He GS, Wang X, Min YH, Pakatchi S, Prasad PN: Chem. Mater.. 2000, 12: 2632. COI number [1:CAS:528:DC%2BD3cXlslChsrc%3D] 10.1021/cm000178kView ArticleGoogle Scholar
- Sharma K, Das S, Maitra A: J. Colloid Interface Sci.. 2005, 284: 358. COI number [1:CAS:528:DC%2BD2MXhvFygtb4%3D] 10.1016/j.jcis.2004.10.006View ArticleGoogle Scholar
- Tan X, Li S: J. Membr. Sci.. 2001, 188: 87. COI number [1:CAS:528:DC%2BD3MXjsFWmtrs%3D] 10.1016/S0376-7388(01)00369-6View ArticleGoogle Scholar
- Lee JJE, Lee J, Yu JH, Kim BC, An K, Hwang Y, Shin CH, Park JG, Kim J: J. Am. Chem. Soc.. 2006, 128: 688. 10.1021/ja0565875View ArticleGoogle Scholar
- Langer R: Nature. 1998, 392: 5. COI number [1:CAS:528:DyaK1cXjtVyls7g%3D]Google Scholar
- Lou XW, Archer LA, Yang Z: Adv. Mater.. 2008, 20: 1. 10.1002/adma.200890067View ArticleGoogle Scholar
- Piao Y, Burns A, Kim J, Wiesner U, Hyeon T: Adv. Funct. Mater.. 2008, 18: 1.Google Scholar
- Barbé C, Bartlett J, Kong L, Finnie K, Lin HQ, Larkin M, Calleja S, Bush A, Calleja G: Adv. Mater.. 2004, 16: 1959. 10.1002/adma.200400771View ArticleGoogle Scholar
- Caturan G, Toso RD, Boninsegna S, Monte RD: J. Mater. Chem.. 2004, 14: 2087. 10.1039/b401450bView ArticleGoogle Scholar
- T. Shiomi, T. Tsunoda, A. Kawai, H. Chiku, F. Mizukami, K. Sakaguchi,Chem.Commun. 5325 (2005). doi: 10.1039/b507736bGoogle Scholar
- Wan Y, Yu S-H: J. Phys. Chem. C. 2008, 112: 3641. COI number [1:CAS:528:DC%2BD1cXitFegur0%3D] 10.1021/jp710990bView ArticleGoogle Scholar
- Fan W, Zhao L: J. Colloid Interface Sci.. 2006, 297: 157. COI number [1:CAS:528:DC%2BD28Xisl2rtb0%3D] 10.1016/j.jcis.2005.10.021View ArticleGoogle Scholar
- Bharali DJ, Klejbor I, Stachowiak EK, Dutta P, Roy I, Kaur N, Bergey EJ, Prasad PN, Stachowiak MK: PNAS. 2005, 102: 11539. COI number [1:CAS:528:DC%2BD2MXoslKiu7o%3D]; Bibcode number [2005PNAS..10211539B] 10.1073/pnas.0504926102View ArticleGoogle Scholar
- Gaikward RM, Sokolov I: J. Dent. Res.. 2008, 87: 980. 10.1177/154405910808701007View ArticleGoogle Scholar
- Caruso F, Caruso RA, Mhwald H: Science. 1998, 282: 111. 10.1126/science.282.5391.1111View ArticleGoogle Scholar
- Chen M, Wu L, Zhou S, You B: Adv. Mater.. 2006, 18: 801. COI number [1:CAS:528:DC%2BD28XjsV2isro%3D] 10.1002/adma.200501528View ArticleGoogle Scholar
- Wang YJ, Caruso F: Chem. Mater.. 2005, 17: 953. COI number [1:CAS:528:DC%2BD2MXps1Krtw%3D%3D] 10.1021/cm0483137View ArticleGoogle Scholar
- van Bommel KJC, Jung JH, Shinkai S: Adv. Mater.. 2001, 13: 1472. 10.1002/1521-4095(200110)13:19<1472::AID-ADMA1472>3.0.CO;2-LView ArticleGoogle Scholar
- Chen JF, Ding HM, Wang JX, Shao L: Biomaterials. 2004, 25: 723. 10.1016/S0142-9612(03)00566-0View ArticleGoogle Scholar
- Ma D, Li M, Patil AJ, Mann S: Adv. Mater.. 2004, 16: 1838. COI number [1:CAS:528:DC%2BD2cXhtVejsLrO] 10.1002/adma.200400351View ArticleGoogle Scholar
- Hubert DHW, Jung M, Frederik PM, Bomans PHH, Meuldijk J, German AL: Adv. Mater.. 2000, 12: 1286. COI number [1:CAS:528:DC%2BD3cXnt1Wlu7c%3D] 10.1002/1521-4095(200009)12:17<1286::AID-ADMA1286>3.0.CO;2-7View ArticleGoogle Scholar
- Hud NV, Vilfan ID: Annu. Biophys. Biomol. Struct.. 2005, 34: 295. COI number [1:CAS:528:DC%2BD2MXlslCku7g%3D] 10.1146/annurev.biophys.34.040204.144500View ArticleGoogle Scholar
- Gelbart WM, Bruinsma RF, Pincus PA, Parsegian VA: Phys. Today. 2000, 53: 38. COI number [1:CAS:528:DC%2BD3cXmvVensro%3D] 10.1063/1.1325230View ArticleGoogle Scholar
- Hud NV, Downing KH: PNAS. 2001, 98: 14925. COI number [1:CAS:528:DC%2BD38Xptlyj]; Bibcode number [2001PNAS...9814925H] 10.1073/pnas.261560398View ArticleGoogle Scholar
- Tsortos A, Nancollas G: J. Colloid Interface Sci.. 2002, 250: 159. COI number [1:CAS:528:DC%2BD38Xjs1agu7c%3D] 10.1006/jcis.2002.8323View ArticleGoogle Scholar
- Molnar F, Rieger J: Langmuir. 2005, 21: 786. COI number [1:CAS:528:DC%2BD2cXhtVOjt73P] 10.1021/la048057cView ArticleGoogle Scholar
- Schweins R, Lindner P, Huber K: Macromolecules. 2003, 36: 9564. COI number [1:CAS:528:DC%2BD3sXpt1Wrurs%3D]; Bibcode number [2003Mamol..36.9564S] 10.1021/ma0347722View ArticleGoogle Scholar
- Göransson A, Hansson P: J. Phys. Chem. B. 2003, 107: 9203. 10.1021/jp027583eView ArticleGoogle Scholar
- Fiers B, Kiefhaber T: J. Am. Chem. Soc.. 2007, 129: 672. 10.1021/ja0666396View ArticleGoogle Scholar
- Huber K, Witte T, Hollmann J, Keuker-Baumann S: J. Am. Chem. Soc.. 2007, 129: 1089. COI number [1:CAS:528:DC%2BD2sXlt1Cguw%3D%3D] 10.1021/ja063368qView ArticleGoogle Scholar
- Numata M, Sugiyasu K, Hasegawa T, Shinkai S: Angew. Chem. Int. Ed.. 2004, 43: 3279. COI number [1:CAS:528:DC%2BD2cXlsF2gt7c%3D] 10.1002/anie.200454009View ArticleGoogle Scholar
- Zhang Y, Jiang M, Zhao J, Wang Z, Dou H, Chen D: Langmuir. 2005, 21: 1531. COI number [1:CAS:528:DC%2BD2MXjs1OhtA%3D%3D] 10.1021/la047912pView ArticleGoogle Scholar
- Tamás G, Viktória T, Benjámin G, Miklós Z: Acta Biomater.. 2008, 4: 733. 10.1016/j.actbio.2007.12.004View ArticleGoogle Scholar
- Fujiwara M, Shiokawa K, Hayashi K, Morigaki K, Nakahara Y: J. Biomed. Mater. Res. Part A. 2007, 81A: 103. COI number [1:CAS:528:DC%2BD2sXjsVSlsbc%3D] 10.1002/jbm.a.31021View ArticleGoogle Scholar
- Fujiwara M, Shiokawa K, Sakakura I, Nakahara Y: Nano. Lett.. 2006, 6: 2925. COI number [1:CAS:528:DC%2BD28Xht1antbfK]; Bibcode number [2006NanoL...6.2925F] 10.1021/nl062298iView ArticleGoogle Scholar
- Mouawia R, Mehdi A, Reyé C, Corriu R: J. Mater. Chem.. 2007, 17: 616. COI number [1:CAS:528:DC%2BD2sXhsVertL8%3D] 10.1039/b618228cView ArticleGoogle Scholar
- Khiterer M, Shea KJ: Nano. Lett.. 2007, 7: 2684. COI number [1:CAS:528:DC%2BD2sXotF2gt7o%3D]; Bibcode number [2007NanoL...7.2684K] 10.1021/nl071087qView ArticleGoogle Scholar
- Paul RTP, McDonnell AP, Kelly CB: Hum. Psychopharmacol. Clin. Exp.. 2004, 19: 477. COI number [1:CAS:528:DC%2BD2cXhtVSjtrfP] 10.1002/hup.614View ArticleGoogle Scholar
- Weitman SD, Lark RH, Coney LR, Fort DW, Frasca V, Zurawski VR, Kamen BA: Cancer Res.. 1992, 52: 3396. COI number [1:CAS:528:DyaK38XksVGltLo%3D]Google Scholar
- Lee H, Char K: Appl. Mater. Interfaces. 2009, 1: 913. COI number [1:CAS:528:DC%2BD1MXktlCqu7o%3D] 10.1021/am900026sView ArticleGoogle Scholar
- Déjugnat C, Sukhorukov GB: Langmuir. 2004, 20: 7265. 10.1021/la049706nView ArticleGoogle Scholar