Journal of Sol-Gel Science and Technology

, Volume 79, Issue 3, pp 447–456 | Cite as

20-nm-sized mesoporous silica nanoparticles with porphyrin photosensitizers for in vitro photodynamic therapy

  • Chiara Mauriello Jimenez
  • Yolanda Galàn Rubio
  • Valentin Saunier
  • David Warther
  • Vanja Stojanovic
  • Laurence Raehm
  • Céline Frochot
  • Philippe Arnoux
  • Marcel Garcia
  • Alain Morère
  • Nadir Bettache
  • Marie Maynadier
  • Philippe Maillard
  • Magali Gary-Bobo
  • Jean-Olivier Durand
Original Paper: Nano-structured materials (particles, fibers, colloids, composites, etc.)


We report the synthesis of 20-nm-sized mesoporous silica nanoparticles encapsulating three different porphyrin photosensitizers (PS). Synthesized by the sol–gel method, in the presence of cetyltrimethylammonium bromide surfactant and tetraorthosilicate as silica source, we developed those nanoparticles with the aim of treating cancer cells using photodynamic therapy. The colloidal stability, due to the PEG-silane chain grafted on the surface, was demonstrated at 37 °C in cell culture medium. Then, nanoparticles were functionalized by silylated squarate mannose and used in MCF-7 breast cancer cells for one-photon therapy. Promising results were obtained after 5 h of incubation.

Graphical Abstract


Porphyrin Mesoporous Silica nanoparticles Functionalization PDT 



Support from the Agence Nationale de la Recherche ANR nanoptPDT and the FEDER Languedoc-Rousssillon project N°41470 are gratefully acknowledged. Laure Lichon of IBMM is thanked for her technical assistance.


  1. 1.
    Knezevic NZ, Durand J-O (2015) Large pore mesoporous silica nanomaterials for application in delivery of biomolecules. Nanoscale 7(6):2199–2209. doi: 10.1039/c4nr06114d CrossRefGoogle Scholar
  2. 2.
    Knezevic NZ, Durand J-O (2015) Targeted treatment of cancer with nanotherapeutics based on mesoporous silica nanoparticles. ChemPlusChem 80(1):26–36. doi: 10.1002/cplu.201402369 CrossRefGoogle Scholar
  3. 3.
    Zhang Y, Yan J, Liu S (2014) Biocompatibility and biomedical applications of functionalized mesoporous silica nanoparticles. Biointerface Res Appl Chem 4 (3):767–775, 769Google Scholar
  4. 4.
    Yang K-N, Zhang C-Q, Wang W, Wang PC, Zhou J-P, Liang X-J (2014) pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment. Cancer Biol Med 11(1):34–43Google Scholar
  5. 5.
    Nadrah P, Planinsek O, Gaberscek M (2014) Stimulus-responsive mesoporous silica particles. J Mater Sci 49(2):481–495CrossRefGoogle Scholar
  6. 6.
    He Q, Shi J (2014) MSN anti-cancer nanomedicines: chemotherapy enhancement, overcoming of drug resistance, and metastasis inhibition. Adv Mater 26(3):391–411CrossRefGoogle Scholar
  7. 7.
    Dave PN, Chopda LV (2014) A review on application of multifunctional mesoporous nanoparticles in controlled release of drug delivery. Mater Sci Forum 781 (Multi-functional nanomaterials and their emerging applications):17–24, 19 ppGoogle Scholar
  8. 8.
    Argyo C, Weiss V, Braeuchle C, Bein T (2014) Multifunctional mesoporous silica nanoparticles as a universal platform for drug delivery. Chem Mater 26(1):435–451CrossRefGoogle Scholar
  9. 9.
    Mai WX, Meng H (2013) Mesoporous silica nanoparticles: a multifunctional nano therapeutic system. Integr Biol 5(1):19–28. doi: 10.1039/c2ib20137b CrossRefGoogle Scholar
  10. 10.
    Mody KT, Popat A, Mahony D, Cavallaro AS, Yu C, Mitter N (2013) Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery. Nanoscale 5(12):5167–5179CrossRefGoogle Scholar
  11. 11.
    Mamaeva V, Sahlgren C, Linden M (2013) Mesoporous silica nanoparticles in medicine-Recent advances. Adv Drug Deliv Rev 65(5):689–702. doi: 10.1016/j.addr.2012.07.018 CrossRefGoogle Scholar
  12. 12.
    Duan R, Xia F, Jiang L (2013) Constructing tunable nanopores and their application in drug delivery. ACS Nano 7(10):8344–8349CrossRefGoogle Scholar
  13. 13.
    Douroumis D, Onyesom I, Maniruzzaman M, Mitchell J (2013) Mesoporous silica nanoparticles in nanotechnology. Crit Rev Biotechnol 33(3):229–245CrossRefGoogle Scholar
  14. 14.
    Chen Y, Chen H, Shi J (2013) In vivo bio-safety evaluations and diagnostic/therapeutic applications of chemically designed mesoporous silica nanoparticles. Adv Mater 25(23):3144–3176. doi: 10.1002/adma.201205292 CrossRefGoogle Scholar
  15. 15.
    Yang P, Gai S, Lin J (2012) Functionalized mesoporous silica materials for controlled drug delivery. Chem Soc Rev 41(9):3679–3698. doi: 10.1039/c2cs15308d CrossRefGoogle Scholar
  16. 16.
    Vivero-Escoto JL, Huxford-Phillips RC, Lin WB (2012) Silica-based nanoprobes for biomedical imaging and theranostic applications. Chem Soc Rev 41(7):2673–2685. doi: 10.1039/c2cs15229k CrossRefGoogle Scholar
  17. 17.
    Tang F, Li L, Chen D (2012) Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater 24(12):1504–1534. doi: 10.1002/adma.201104763 CrossRefGoogle Scholar
  18. 18.
    Lin Y-S, Hurley KR, Haynes CL (2012) Critical considerations in the biomedical use of mesoporous silica nanoparticles. J Phys Chem Lett 3(3):364–374CrossRefGoogle Scholar
  19. 19.
    Li Z, Barnes JC, Bosoy A, Stoddart JF, Zink JI (2012) Mesoporous silica nanoparticles in biomedical applications. Chem Soc Rev 41(7):2590–2605. doi: 10.1039/c1cs15246g CrossRefGoogle Scholar
  20. 20.
    Asefa T, Tao Z (2012) Biocompatibility of mesoporous silica nanoparticles. Chem Res Toxicol 25(11):2265–2284. doi: 10.1021/tx300166u CrossRefGoogle Scholar
  21. 21.
    Yang Y-W (2011) Towards biocompatible nanovalves based on mesoporous silica nanoparticles. Medchemcomm 2(11):1033–1049. doi: 10.1039/c1md00158b CrossRefGoogle Scholar
  22. 22.
    Popat A, Hartono SB, Stahr F, Liu J, Qiao SZ, Lu GQ (2011) Mesoporous silica nanoparticles for bioadsorption, enzyme immobilisation, and delivery carriers. Nanoscale 3(7):2801–2818. doi: 10.1039/c1nr10224a CrossRefGoogle Scholar
  23. 23.
    He Q, Shi J (2011) Mesoporous silica nanoparticle based nano drug delivery systems: synthesis, controlled drug release and delivery, pharmacokinetics and biocompatibility. J Mater Chem 21(16):5845–5855CrossRefGoogle Scholar
  24. 24.
    Vivero-Escoto JL, Slowing II, Trewyn BG, Lin VSY (2010) Mesoporous silica nanoparticles for intracellular controlled drug delivery. Small 6(18):1952–1967CrossRefGoogle Scholar
  25. 25.
    Coti KK, Belowich ME, Liong M, Ambrogio MW, Lau YA, Khatib HA, Zink JI, Khashab NM, Stoddart JF (2009) Mechanised nanoparticles for drug delivery. Nanoscale 1(1):16–39CrossRefGoogle Scholar
  26. 26.
    Slowing II, Vivero-Escoto JL, Wu C-W, Lin VSY (2008) Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev 60(11):1278–1288CrossRefGoogle Scholar
  27. 27.
    Trewyn BG, Slowing II, Giri S, Chen H-T, Lin VSY (2007) Synthesis and functionalization of a mesoporous silica nanoparticle based on the sol-gel process and applications in controlled release. Acc Chem Res 40(9):846–853CrossRefGoogle Scholar
  28. 28.
    Trewyn BG, Giri S, Slowing II, Lin VSY (2007) Mesoporous silica nanoparticle based controlled release, drug delivery, and biosensor systems. Chem Commun 31:3236–3245CrossRefGoogle Scholar
  29. 29.
    Slowing II, Trewyn BG, Giri S, Lin VSY (2007) Mesoporous silica nanoparticles for drug delivery and biosensing applications. Adv Funct Mater 17(8):1225–1236CrossRefGoogle Scholar
  30. 30.
    Wu S-H, Mou C-Y, Lin H-P (2013) Synthesis of mesoporous silica nanoparticles. Chem Soc Rev 42(9):3862–3875. doi: 10.1039/c3cs35405a CrossRefGoogle Scholar
  31. 31.
    Slowing II, Vivero-Escoto JL, Trewyn BG, Lin VSY (2010) Mesoporous silica nanoparticles: structural design and applications. J Mater Chem 20(37):7924–7937CrossRefGoogle Scholar
  32. 32.
    Hoshikawa Y, Yabe H, Nomura A, Yamaki T, Shimojima A, Okubo T (2010) Mesoporous silica nanoparticles with remarkable stability and dispersibility for antireflective coatings. Chem Mater 22(1):12–14. doi: 10.1021/cm902239a CrossRefGoogle Scholar
  33. 33.
    Huh S, Chen H-T, Wiench JW, Pruski M, Lin VSY (2005) Cooperative catalysis by general acid and base bifunctionalized mesoporous silica nanospheres. Angew Chem Int Ed Engl 44(12):1826–1830CrossRefGoogle Scholar
  34. 34.
    Lei J, Wang L, Zhang J (2010) Ratiometric pH sensor based on mesoporous silica nanoparticles and Foerster resonance energy transfer. Chem Commun (Cambridge, UK) 46(44):8445–8447CrossRefGoogle Scholar
  35. 35.
    Mondragon L, Mas N, Ferragud V, de la Torre C, Agostini A, Martinez-Manez R, Sancenon F, Amoros P, Perez-Paya E, Orzaez M (2014) Enzyme- responsive intracellular- controlled release using silica mesoporous nanoparticles capped with e- poly- l- lysine. Chem Eur J 20(18):5271–5281. doi: 10.1002/chem.201400148 CrossRefGoogle Scholar
  36. 36.
    Chouikrat R, Seve A, Vanderesse R, Benachour H, Barberi-Heyob M, Richeter S, Raehm L, Durand JO, Verelst M, Frochot C (2012) Non polymeric nanoparticles for photodynamic therapy applications: recent developments. Curr Med Chem 19(6):781–792CrossRefGoogle Scholar
  37. 37.
    Couleaud P, Morosini V, Frochot C, Richeter S, Raehm L, Durand JO (2010) Silica-based nanoparticles for photodynamic therapy applications. Nanoscale 2(7):1083–1095. doi: 10.1039/c0nr00096e CrossRefGoogle Scholar
  38. 38.
    Yamamoto E, Kitahara M, Tsumura T, Kuroda K (2014) Preparation of size-controlled monodisperse colloidal mesoporous silica nanoparticles and fabrication of colloidal crystals. Chem Mater 26(9):2927–2933. doi: 10.1021/cm500619p CrossRefGoogle Scholar
  39. 39.
    Pan L, Liu J, He Q, Wang L, Shi J (2013) Overcoming multidrug resistance of cancer cells by direct intranuclear drug delivery using TAT-conjugated mesoporous silica nanoparticles. Biomaterials 34(11):2719–2730. doi: 10.1016/j.biomaterials.2012.12.040 CrossRefGoogle Scholar
  40. 40.
    Yi Z, Dumee LF, Garvey CJ, Feng C, She F, Rookes JE, Mudie S, Cahill DM, Kong L (2015) A new insight into growth mechanism and kinetics of mesoporous silica nanoparticles by in situ small angle X-ray scattering. Langmuir 31(30):8478–8487. doi: 10.1021/acs.langmuir.5b01637 CrossRefGoogle Scholar
  41. 41.
    Urata C, Aoyama Y, Tonegawa A, Yamauchi Y, Kuroda K (2009) Dialysis process for the removal of surfactants to form colloidal mesoporous silica nanoparticles. Chem Commun 34:5094–5096. doi: 10.1039/b908625k CrossRefGoogle Scholar
  42. 42.
    Qiao Z-A, Zhang L, Guo M, Liu Y, Huo Q (2009) Synthesis of mesoporous silica nanoparticles via controlled hydrolysis and condensation of silicon alkoxide. Chem Mater 21(16):3823–3829. doi: 10.1021/cm901335k CrossRefGoogle Scholar
  43. 43.
    Lu F, Wu SH, Hung Y, Mou CY (2009) Size effect on cell uptake in well-suspended, uniform mesoporous silica nanoparticles. Small 5(12):1408–1413. doi: 10.1002/smll.200900005 CrossRefGoogle Scholar
  44. 44.
    Ma K, Werner-Zwanziger U, Zwanziger J, Wiesner U (2013) Controlling growth of ultrasmall sub-10 nm fluorescent mesoporous silica nanoparticles. Chem Mater 25(5):677–691. doi: 10.1021/cm303242h CrossRefGoogle Scholar
  45. 45.
    Ma K, Sai H, Wiesner U (2012) Ultrasmall sub-10 nm near-infrared fluorescent mesoporous silica nanoparticles. J Am Chem Soc 134(32):13180–13183. doi: 10.1021/ja3049783 CrossRefGoogle Scholar
  46. 46.
    Wu M, Meng Q, Chen Y, Du Y, Zhang L, Li Y, Zhang L, Shi J (2015) Large-pore ultrasmall mesoporous organosilica nanoparticles: micelle/precursor co-templating assembly and nuclear-targeted gene delivery. Adv Mater (Weinheim, Ger) 27(2):215–222. doi: 10.1002/adma.201404256 CrossRefGoogle Scholar
  47. 47.
    Pan L, Liu J, He Q, Shi J (2014) MSN-mediated sequential vascular-to-cell nuclear-targeted drug delivery for efficient tumor regression. Adv Mater (Weinheim, Ger) 26(39):6742–6748. doi: 10.1002/adma.201402752 CrossRefGoogle Scholar
  48. 48.
    Li Z-Y, Liu Y, Hu J-J, Xu Q, Liu L-H, Jia H-Z, Chen W-H, Lei Q, Rong L, Zhang X-Z (2014) Stepwise-acid-active multifunctional mesoporous silica nanoparticles for tumor-specific nucleus-targeted drug delivery. ACS Appl Mater Interfaces 6(16):14568–14575CrossRefGoogle Scholar
  49. 49.
    Pan L, Liu J, Shi J (2014) Intranuclear photosensitizer delivery and photosensitization for enhanced photodynamic therapy with ultralow irradiance. Adv Funct Mater 24(46):7318–7327. doi: 10.1002/adfm.201402255 CrossRefGoogle Scholar
  50. 50.
    Brevet D, Gary-Bobo M, Raehm L, Richeter S, Hocine O, Amro K, Loock B, Couleaud P, Frochot C, Morere A, Maillard P, Garcia M, Durand JO (2009) Mannose-targeted mesoporous silica nanoparticles for photodynamic therapy. Chem Commun 12:1475–1477. doi: 10.1039/b900427k CrossRefGoogle Scholar
  51. 51.
    Warther D, Jimenez CM, Raehm L, Gerardin C, Durand J-O, Morere A, El Cheikh K, Gallud A, Gary-Bobo M, Maynadier M, Garcia M (2014) Small sized mesoporous silica nanoparticles functionalized with mannose for retinoblastoma cell imaging. RSC Adv 4(70):37171–37179. doi: 10.1039/c4ra05310a CrossRefGoogle Scholar
  52. 52.
    Hocine O, Gary-Bobo M, Brevet D, Maynadier M, Fontanel S, Raehm L, Richeter S, Loock B, Couleaud P, Frochot C, Charnay C, Derrien G, Smaihi M, Sahmoune A, Morere A, Maillard P, Garcia M, Durand J-O (2010) Silicalites and mesoporous silica nanoparticles for photodynamic therapy. Int J Pharm 402(1–2):221–230CrossRefGoogle Scholar
  53. 53.
    De Rosa M, Crutchley RJ (2002) Photosensitized singlet oxygen and its applications. Coord Chem Rev 233–234:351–371. doi: 10.1016/S0010-8545(02)00034-6 Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Chiara Mauriello Jimenez
    • 1
  • Yolanda Galàn Rubio
    • 1
  • Valentin Saunier
    • 1
  • David Warther
    • 1
  • Vanja Stojanovic
    • 2
  • Laurence Raehm
    • 1
  • Céline Frochot
    • 4
  • Philippe Arnoux
    • 4
  • Marcel Garcia
    • 2
  • Alain Morère
    • 2
  • Nadir Bettache
    • 2
  • Marie Maynadier
    • 5
  • Philippe Maillard
    • 3
  • Magali Gary-Bobo
    • 2
  • Jean-Olivier Durand
    • 1
  1. 1.UMR 5253, CC 1701 Equipe Ingénierie Moléculaire et Nano-objetsInstitut Charles Gerhardt MontpellierMontpellier Cedex 05France
  2. 2.UMR 5247Institut de Biomolécules Max MousseronMontpellier Cedex 05France
  3. 3.CMIB UMR 9187-U1196, Centre UniversitaireInstitut Curie-RechercheOrsayFrance
  4. 4.Laboratoire Réactions et Génie de Procédés, UMR 7274CNRS-Université de LorraineNancyFrance
  5. 5.NanoMedSynMontpellier Cedex 05France

Personalised recommendations