Improving structural stability of water-dispersed MCM-41 silica nanoparticles through post-synthesis pH aging process

  • Mathieu Varache
  • Igor Bezverkhyy
  • Florence Bouyer
  • Rémi Chassagnon
  • Florence Baras
  • Frédéric Bouyer
Research Paper


The colloidal and structural stabilities of MCM-41 mesoporous silica nanoparticles (MSNs) are of great importance in order to prepare optimal nanovectors. In this paper, MSNs (approximatively 160 nm in diameter) were synthesized using n-cetyltrimethylammonium bromide as a template and tetraethyl orthosilicate as a silica source under high N2 flow (MSN/N2) to obtain stable dispersions in water. The degradation of the porous nanoparticles was investigated by immersion in water. The morphology and the porous structure were studied by TEM, XRD, N2 sorption, and 29Si MAS NMR and were compared to that of MSNs prepared in ambient air (MSN/air). The volumetric properties of the MSN/N2 after 1 day in water were drastically more decreased than MSN/air (a pore volume decrease of 85 % for MSN/N2 and 59 % for MSN/air) and the 2D-hexagonal porous structure was totally lost. Furthermore, synthesizing MSNs under a high N2 flow leads to a decrease in the synthesis yield (45 % MSN/N2 and 75 % for MSN/air). The lower structural stability of the MSN/N2 is explained by the lower polycondensation degree of the MSN/N2 observed by 29Si MAS NMR (Q4/Q3 = 0.86 for MSN/N2 and 1.61 for MSN/air) and the lower silica molar ratio in the nanomaterials (SiO2/CTA = 3.9 for MSN/N2 7.1 for MSN/air). This allows for enhanced solubilization of silica in water. Four strategies were hence evaluated in order to reinforce the porous structure of the MSNs. Among them, the most efficient route was based on a pH adjustment of the colloidal suspension (pH 7.5) after 2 h of synthesis without any purification and while keeping a N2 static atmosphere (called MSN/N2/7.5). After 1 day in water, the volumetric and structural properties of MSN/N2/7.5 were similar to that obtained for MSN/air. The improvement of the stability arose as a result of the increase in the silica condensation (Q4/Q3 = 1.58) and silica molar ratio in the nanomaterials (SiO2/CTA = 6.8). After the post-treatment, the silica framework condensation is improved while keeping the colloidal stability, thus allowing further functionalization and/or drug loading. Cytotoxicity assays using SW480 cancer cells show a greater improvement in the cell viability.

Graphical Abstract


Mesoporous silica nanoparticles MCM-41 Degradation Stability Aging process Condensation 



This study was supported by the Conseil Régional de Bourgogne under Contract No. 9201AAO03S05201 and by the 3MIM agreement (CNRS, uB and Conseil Régional de Bourgogne). We acknowledge Dr N. Geoffroy for his advices in XRD characterizations.

Compliance with ethical standards

Conflict of interest

The authors of the manuscript certify that there is no conflict of interest among the authors in publishing this paper.

Supplementary material

11051_2015_3147_MOESM1_ESM.docx (255 kb)
Supplementary material 1 (DOCX 255 kb)


  1. Boudier A, Aubert-Pouessel A, Mebarek N, Chavanieu A, Quentin J, Martire D et al (2011) Development of tripartite polyion micelles for efficient peptide delivery into dendritic cells without altering their plasticity. J Control Release 154:156–163CrossRefGoogle Scholar
  2. Brevet D, Gary-Bobo M, Raehm L, Richeter S, Hocine O, Amro K et al (2009) Mannose-targeted mesoporous silica nanoparticles for photodynamic therapy. Chem Commun 12:1475–1477CrossRefGoogle Scholar
  3. Brinker CJ, Scherer GW (1990) Sol–gel science: the physics and chemistry of sol–gel processing. Academic Press, LondonGoogle Scholar
  4. Broyer M, Valange S, Bellat JP, Bertrand O, Weber G, Gabelica Z (2002) Influence of aging, thermal, hydrothermal, and mechanical treatments on the porosity of MCM-41 mesoporous silica. Langmuir 18:5083–5091CrossRefGoogle Scholar
  5. Cai Q, Lin W-Y, Xiao F-S, Pang W-Q, Chen X-H, Zou B-S (1999) The Preparation of Highly Ordered MCM-41 with Extremely Low Surfactant Concentration. Microporous Mesoporous Mater 32:1–15CrossRefGoogle Scholar
  6. Cai Q, Luo Z-S, Pang W-Q, Fan Y-W, Chen X-H, Cui F-Z (2001) Dilute solution routes to various controllable morphologies of MCM-41 silica with a basic medium. Chem Mater 13:258–263CrossRefGoogle Scholar
  7. Cebrian V, Yaguee C, Arruebo M, Martin-Saavedra FM, Santamaria J, Vilaboa N (2011) On the role of the colloidal stability of mesoporous silica nanoparticles as gene delivery vectors. J Nanopart Res 13:4097–4108CrossRefGoogle Scholar
  8. Chen L, Horiuchi T, Mori T, Maeda K (1999) Postsynthesis hydrothermal restructuring of M41S mesoporous molecular sieves in water. J Phys Chem B 103:1216–1222CrossRefGoogle Scholar
  9. Chong ASM, Zhao XS, Kustedjo AT, Qiao SZ (2004) Functionalization of large-pore mesoporous silicas with organosilanes by direct synthesis. Microporous Mesoporous Mater 72:33–42CrossRefGoogle Scholar
  10. Ciesla U, Schüth F (1999) Ordered mesoporous materials. Microporous Mesoporous Mater 27:131–149CrossRefGoogle Scholar
  11. Descalzo AB, Martínez-Máñez R, Sancenón F, Hoffmann K, Rurack K (2006) The supramolecular chemistry of organic-inorganic hybrid materials. Angew Chem Int Ed 45:5924–5948CrossRefGoogle Scholar
  12. Doyle A, Hodnett BK (2003) Stability of MCM-48 in aqueous solution as a function of pH. Microporous Mesoporous Mater 63:53–57CrossRefGoogle Scholar
  13. Du X, He J (2010) Elaborate control over the morphology and structure of mercapto-functionalized mesoporous silicas as multipurpose carriers. Dalton Trans 39:9063–9072CrossRefGoogle Scholar
  14. Du Y, Lan X, Liu S, Ji Y, Zhang Y, Zhang W et al (2008) The search of promoters for silica condensation and rational synthesis of hydrothermally stable and well ordered mesoporous silica materials with high degree of silica condensation at conventional temperature. Microporous Mesoporous Mater 112:225–234CrossRefGoogle Scholar
  15. Edler KJ, White JW (1997) Further improvements in the long-range order of MCM-41 materials. Chem Mater 9:1226–1233CrossRefGoogle Scholar
  16. Eurov DA, Kurdyukov DA, Kirilenko DA, Kukushkina JA, Nashchekin AV, Smirnov AN et al (2015) Core-shell monodisperse spherical mSiO(2)/Gd2O3:Eu3 + @mSiO(2) particles as potential multifunctional theranostic agents. J Nanopart Res 17:82CrossRefGoogle Scholar
  17. Finnie KS, Waller DJ, Perret FL, Krause-Heuer AM, Lin HQ, Hanna JV et al (2009) Biodegradability of sol–gel silica microparticles for drug delivery. J Sol–Gel Sci Technol 49:12–18CrossRefGoogle Scholar
  18. Galarneau A, Driole MF, Petitto C, Chiche B, Bonelli B, Armandi M et al (2005) Effect of post-synthesis treatment on the stability and surface properties of MCM-48 silica. Microporous Mesoporous Mater 83:172–180CrossRefGoogle Scholar
  19. Gary-Bobo M, Mir Y, Rouxel C, Brevet D, Hocine O, Maynadier M et al (2012) Multifunctionalized mesoporous silica nanoparticles for the in vitro treatment of retinoblastoma: drug delivery, one and two-photon photodynamic therapy. Int J Pharm 432:99–104CrossRefGoogle Scholar
  20. Goel S, Chen F, Hong H, Valdovinos HF, Hernandez R, Shi SX et al (2014) VEGF(121)-conjugated mesoporous silica nanoparticle: a tumor targeted drug delivery system. ACS Appl Mater Interfaces 6:21677–21685CrossRefGoogle Scholar
  21. Gouze B, Cambedouzou J, Parres-Maynadie S, Rebiscoul D (2014) How hexagonal mesoporous silica evolves in water on short and long term: role of pore size and silica wall porosity. Microporous Mesoporous Mater 183:168–176CrossRefGoogle Scholar
  22. He Q, Zhang Z, Gao Y, Shi J, Li Y (2009) Intracellular localization and cytotoxicity of spherical mesoporous silica nano- and microparticles. Small 5:2722–2729CrossRefGoogle Scholar
  23. He Q, Shi J, Chen F, Zhu M, Zhang L (2010) An anticancer drug delivery system based on surfactant-templated mesoporous silica nanoparticles. Biomaterials 31:3335–3346CrossRefGoogle Scholar
  24. Hocine O, Gary-Bobo M, Brevet D, Maynadier M, Fontanel S, Raehm L et al (2010) Silicalites and mesoporous silica nanoparticles for photodynamic therapy. Int J Pharm 402:221–230CrossRefGoogle Scholar
  25. Huh S, Wiench JW, Yoo J-C, Pruski M, Lin VS-Y (2003) Organic functionalization and morphology control of mesoporous silicas via a co-condensation synthesis method. Chem Mater 15:4247–4256CrossRefGoogle Scholar
  26. Iler RK (1979) The chemistry of silica. Wiley, New YorkGoogle Scholar
  27. Kecht J, Schlossbauer A, Bein T (2008) Selective functionalization of the outer and inner surfaces in mesoporous silica nanoparticles. Chem Mater 20:7207–7214CrossRefGoogle Scholar
  28. Kim JM, Ryoo R (1996) Disintegration of mesoporous structures of MCM-41 and MCM-48 in Water. B Korean Chem Soc 17:66–68Google Scholar
  29. Landau MV, Varkey SP, Herskowitz M, Regev O, Pevzner S, Sen T et al (1999) Wetting stability of Si-MCM-41 mesoporous material in neutral, acidic and basic aqueous solutions. Microporous Mesoporous Mater 33:149–163CrossRefGoogle Scholar
  30. Lang N, Tuel A (2004) A fast and efficient ion-exchange procedure to remove surfactant molecules from MCM-41 materials. Chem Mater 16:1961–1966CrossRefGoogle Scholar
  31. Lastoskie C, Gubbins KE, Quirke N (1993) Pore-size distribution analysis of microporous carbons—a density-functional theory approach. J Phys Chem 97:4786–4796CrossRefGoogle Scholar
  32. Lin HP, Mou CY (2002) Salt effect in post-synthesis hydrothermal treatment of MCM-41. Microporous Mesoporous Mater 55:69–80CrossRefGoogle Scholar
  33. Massiot D, Fayon F, Capron M, King I, Le Calvé S, Alonso B et al (2002) Modelling one- and two-dimensional solid-state NMR spectra. Magn Reson Chem 40:70–76CrossRefGoogle Scholar
  34. Mishra AK, Pandey H, Agarwal V, Ramteke PW, Pandey AC (2014) Nanoengineered mesoporous silica nanoparticles for smart delivery of doxorubicin. J Nanopart Res 16:2515CrossRefGoogle Scholar
  35. Misra V, Rahman Q, Viswanathan PN (1983) Binding of silicic acid by proteins and its relation to toxicity of silicate dusts. J Appl Toxicol 3:135–138CrossRefGoogle Scholar
  36. Pasqua L, Testa F, Aiello R, Renzo FD, Fajula F (2001) Influence of pH and nature of the anion on the synthesis of pure and iron-containing mesoporous silica. Microporous Mesoporous Mater 44–45:111–117CrossRefGoogle Scholar
  37. Pourjavadi A, Tehrani ZM, Mahmoudi N (2015) The effect of protein corona on doxorubicin release from the magnetic mesoporous silica nanoparticles with polyethylene glycol coating. J Nanopart Res 17:197CrossRefGoogle Scholar
  38. Rashidi L, Vasheghani-Farahani E, Soleimani M, Atashi A, Rostami K, Gangi F et al (2014) A cellular uptake and cytotoxicity properties study of gallic acid-loaded mesoporous silica nanoparticles on Caco-2 cells. J Nanopart Res 16:2285CrossRefGoogle Scholar
  39. Ribeiro Carrott MML, Estêvão Candeias AJ, Carrott PJM, Unger KK (1999) Evaluation of the stability of pure silica MCM-41 toward water vapor. Langmuir 15:8895–8901CrossRefGoogle Scholar
  40. Rouxhet PG, Genet MJ (2011) XPS analysis of bio-organic systems. Surf Interface Anal 43:1453–1470CrossRefGoogle Scholar
  41. Ryoo R, Jun S (1997) Improvement of hydrothermal stability of MCM-41 using salt effects during the crystallization process. J Phys Chem B 101:317–320CrossRefGoogle Scholar
  42. Ryoo R, Kim JM (1995) Structural order in MCM-41 controlled by shifting silicate polymerization equilibrium. J Chem Soc Chem Commun 7:711–712CrossRefGoogle Scholar
  43. Sing KSW, Everett DH, Haul RAW, Moscou L, Pierotti J, Rouquerol J et al (1985) Reporting physisorption data for gas solid systems with special reference to the determination of surface-area and porosity (Recommendations 1984). Pure Appl Chem 57:603–619CrossRefGoogle Scholar
  44. Slowing II, Vivero-Escoto JL, Trewyn BG, Lin VS-Y (2010) Mesoporous silica nanoparticles: structural design and applications. J Mater Chem 20:7924–7937CrossRefGoogle Scholar
  45. Taylor KML, Kim JS, Rieter WJ, An H, Lin W, Lin W (2008) Mesoporous silica nanospheres as highly efficient MRI contrast agents. J Am Chem Soc 130:2154–2155CrossRefGoogle Scholar
  46. Tompkins JT, Mokaya R (2014) Steam stable mesoporous silica MCM-41 stabilized by trace amounts of Al. ACS Appl Mater Interfaces 6:1902–1908CrossRefGoogle Scholar
  47. Tu HL, Lin YS, Lin HY, Hung Y, Lo LW, Chen YF et al (2009) In vitro studies of functionalized mesoporous silica nanoparticles for photodynamic therapy. Adv Mater 21:172–177CrossRefGoogle Scholar
  48. Varache M (2014) Synthesis of mesoporous silica nanoparticles (MSNs) and encapsulation of cisplatin for targeted cancer therapies. Dissertation, University of Burgundy, FranceGoogle Scholar
  49. Varache M, Bezverkhyy I, Saviot L, Bouyer F, Baras F, Bouyer F (2015) Optimization of MCM-41 type silica nanoparticles for biological applications: control of size and absence of aggregation and cell cytotoxicity. J Non-Cryst Solids 408:87–97CrossRefGoogle Scholar
  50. Vivero-Escoto JL, Slowing II, Trewyn BG, Lin VSY (2010a) Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small 6:1952–1967CrossRefGoogle Scholar
  51. Vivero-Escoto JL, Trewyn BG, Lin VSY (2010b) Mesoporous silica nanoparticles: synthesis and applications. In: Cao G, Zhang Q, Brinker CJ (eds) Annual review of nano research. World Scientific Publishing, New Jersey, pp 191–231Google Scholar
  52. Walcarius A, Etienne M, Lebeau B (2003) Rate of access to the binding sites in organically modified silicates. 2. Ordered mesoporous silicas grafted with amine or thiol groups. Chem Mater 15:2161–2173CrossRefGoogle Scholar
  53. Xu B, Ju Y, Song G, Cui Y (2013) tLyP-1-Conjugated mesoporous silica nanoparticles for tumor targeting and penetrating hydrophobic drug delivery. J Nanopart Res 15:2105CrossRefGoogle Scholar
  54. Zhang H, Wu J, Zhou L, Zhang D, Qi L (2007) Facile synthesis of monodisperse microspheres and gigantic hollow shells of mesoporous silica in mixed water-ethanol solvents. Langmuir 23:1107–1113CrossRefGoogle Scholar
  55. Zhao XS, Audsley F, Lu GQ (1998) Irreversible change of pore structure of MCM-41 upon hydration at room temperature. J Phys Chem B 102:4143–4146CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  • Mathieu Varache
    • 1
  • Igor Bezverkhyy
    • 1
  • Florence Bouyer
    • 2
  • Rémi Chassagnon
    • 1
  • Florence Baras
    • 1
  • Frédéric Bouyer
    • 1
  1. 1.Laboratoire Interdisciplinaire Carnot de BourgogneUMR 6303 CNRS-Université Bourgogne Franche-ComtéDijon CedexFrance
  2. 2.Inserm U866, Equipe Chimiothérapie, métabolisme des lipides et réponse immunitaire anti-tumoraleDijon CedexFrance

Personalised recommendations