Analytical and Bioanalytical Chemistry

, Volume 408, Issue 2, pp 535–544 | Cite as

Fourier transform infrared spectroscopy (FTIR) characterization of the interaction of anti-cancer photosensitizers with dendrimers

  • Monika Dabrzalska
  • Nuria Benseny-Cases
  • Ramon Barnadas-Rodríguez
  • Serge Mignani
  • Maria Zablocka
  • Jean-Pierre Majoral
  • Maria Bryszewska
  • Barbara Klajnert-Maculewicz
  • Josep CladeraEmail author
Research Paper


The systemic or local administration of a photosensitizer for photodynamic therapy is highly limited by poor selectivity, rapid deactivation and long-lasting skin toxicity due to unfavorable biodistribution. Drug delivery systems based on nanocarriers may help specific and effective delivery of photosensitizers. In the present paper, the interaction of two photosensitizers, methylene blue and rose bengal, with phosphorous cationic and anionic dendrimers as potential nanocarriers, has been characterized. A novel method is presented based on the analysis of the infrared spectra of mixtures of photosensitizer and dendrimer. The capacity of dendrimers to bind the photosensitizers has been evaluated by obtaining the corresponding binding curves. It is shown that methylene blue interacts with both cationic and anionic dendrimers, whereas rose bengal only binds to the cationic ones. Dendrimers are shown to be potential nanocarriers for a specific delivery of both photosensitizers.


Phosphorus dendrimer Rose bengal Methylene blue Infrared spectroscopy Dendrimer-photosensitizer interactions 



This study was funded by the project “Phosphorus dendrimers as carriers of photosensitizers in photodynamic therapy and its combination with hyperthermia in in vitro studies” operated within the Foundation for Polish Science VENTURES Programme (Project VENTURES number VENTURES/2013-11/3) co-financed by the EU European Regional Development Fund and by the grant HARMONIA “Studying phosphorus dendrimers as systems transporting photosensitizers” no. UMO-2013/08/M/NZ1/00761 supported by National Science Centre.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Torchilin VP (2006) Multifunctional nanocarriers. Adv Drug Deliv Rev 58:1532–1555CrossRefGoogle Scholar
  2. 2.
    Foster TH, Giesselman BR, Hu R, Kenney ME, Mitra S (2010) Intratumor administration of the photosensitizer Pc 4 affords photodynamic therapy efficacy and selectivity at short drug-light intervals. Transl Oncol 3:135–141CrossRefGoogle Scholar
  3. 3.
    Yano S, Hirohara S, Obata M, Hagiya Y, Ogura S, Ikeda A, Kataoka H, Tanaka M, Joh T (2011) Current states and future views in photodynamic therapy. J Photochem Photobiol C 12:46–67CrossRefGoogle Scholar
  4. 4.
    Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q (1998) Photodynamic therapy. J Natl Cancer Inst 90:889–905CrossRefGoogle Scholar
  5. 5.
    Konan YN, Gurny R, Alleman E (2002) State of the art in the delivery of photosensitizers for photodynamic therapy. J Photochem Photobiol B 66:89–106CrossRefGoogle Scholar
  6. 6.
    O’Connor AE, Gallagher WM, Byrne AT (2009) Porphyrin and nonporphyrin photosensitizers in oncology: preclinical and clinical advances in photodynamic therapy. Photochem Photobiol 85:1053–1074CrossRefGoogle Scholar
  7. 7.
    Saboktakin MR, Tabatabaie RM, Maharramov A, Ramazanov MA (2011) Synthesis and in vitro studies of biodegradable modified chitosan nanoparticles for photodynamic treatment of cancer. Int J Biol Macromol 49:1059–1065CrossRefGoogle Scholar
  8. 8.
    Kano A, Taniwaki Y, Nakamura I, Shimada N, Moriyama K, Maruyama A (2013) Tumor delivery of Photofrin(R) by PLL-g-PEG for photodynamic therapy. J Control Release 167:315–321CrossRefGoogle Scholar
  9. 9.
    Derycke ASL, De Witte PAM (2004) Liposomes for photodynamic therapy. Adv Drug Deliv Rev 56:17–30CrossRefGoogle Scholar
  10. 10.
    Vivero-Escoto JL, Vegaab DL (2014) Stimuli-responsive protoporphyrin IX silica-based nanoparticles for photodynamic therapy in vitro. RSC Adv 4:14400–14407CrossRefGoogle Scholar
  11. 11.
    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, Smaïhi M, Sahmoune A, Morère A, Maillard P, Garcia M, Durand JO (2010) Silicalites and mesoporous silica nanoparticles for photodynamic therapy. Int J Pharm 402:221–230CrossRefGoogle Scholar
  12. 12.
    Camerin M, Magaraggia M, Soncin M, Jori G, Moreno M, Chambrier I, Cook MJ, Russell DA (2010) The in vivo efficacy of phthalocyanine-nanoparticle conjugates for the photodynamic therapy of amelanotic melanoma. Eur J Cancer 46:1910–1918CrossRefGoogle Scholar
  13. 13.
    Ol’shevskaya VA, Savchenko AN, Zaitsev AV, Kononova EG, Petrovskii PV, Ramonova AA, Tatarskiy VV Jr, Moisenovich MM, Kalinin VN, Shtil AA (2009) Novel metal complexes of boronated chlorine e6 for photodynamic therapy. J Organomet Chem 694:1632–1637CrossRefGoogle Scholar
  14. 14.
    Klajnert B, Bryszewska M (2001) Dendrimers: properties and applications. Acta Biochim Pol 48:199–208Google Scholar
  15. 15.
    El Kazzouli S, El Brahmi N, Mignani S, Bousmina M, Zablocka M, Majoral JP (2012) From metallodrugs to metallodendrimers for nanotherapy in oncology: a concise overview. Curr Med Chem 19:4995–5010CrossRefGoogle Scholar
  16. 16.
    Mignani S, El Kazzouli S, Bousmina M, Majoral JP (2013) Dendrimer space concept for innovative nanomedicine: a futuristic vision for medicinal chemistry. Prog Polym Sci 38:993–1008CrossRefGoogle Scholar
  17. 17.
    Mignani S, El Kazzouli S, Bousmina M, Majoral JP (2013) Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview. Adv Drug Deliv Rev 65:1316–1330CrossRefGoogle Scholar
  18. 18.
    Klajnert B, Rozanek M, Bryszewska M (2012) Dendrimers in photodynamic therapy. Curr Med Chem 19:4903–4912CrossRefGoogle Scholar
  19. 19.
    Ihre HR, Padilla De Jesús O, Szoka FC Jr, Fréchet JMJ (2002) Polyester dendritic systems for drug delivery applications: design, synthesis, and characterization. Bioconjug Chem 13:443–452CrossRefGoogle Scholar
  20. 20.
    Patri AK, Kukowska-Latallo JF, Baker JR Jr (2005) Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Adv Drug Deliv Rev 57:2203–2214CrossRefGoogle Scholar
  21. 21.
    Bhadra D, Bhadra S, Jain S, Jain NK (2003) A PEGylated dendritic nanoparticulate carrier of fluorouracil. Int J Pharm 257:111–112CrossRefGoogle Scholar
  22. 22.
    Kojima C, Toi Y, Harada A, Kono K (2007) Preparation of poly(ethylene glycol)-attached dendrimers encapsulating photosensitizers for application to photodynamic therapy. Bioconjug Chem 18:663–670CrossRefGoogle Scholar
  23. 23.
    Herlambang S, Kumagai M, Nomoto T, Horie S, Fukushima S, Oba M, Miyazaki K, Morimoto Y, Nishiyama N, Kataoka K (2011) Disulfide crosslinked polyion complex micelles encapsulating dendrimer phthalocyanine directed to improved efficiency of photodynamic therapy. J Control Release 155:449–457CrossRefGoogle Scholar
  24. 24.
    Nishiyama N, Nakagishi Y, Morimoto Y, Lai PS, Miyazaki K, Urano K, Horie S, Kumagai M, Fukushima S, Cheng Y, Jang WD, Kikuchi M, Kataoka K (2009) Enhanced photodynamic cancer treatment by supramolecular nanocarriers charged with dendrimer phthalocyanine. J Control Release 133:245–251CrossRefGoogle Scholar
  25. 25.
    Zhang GD, Harada A, Nishiyama N, Jiang DL, Koyama H, Aida T, Kataoka K (2003) Polyion complex micelles entrapping cationic dendrimer porphyrin: effective photosensitizer for photodynamic therapy of cancer. J Control Release 93:141–150CrossRefGoogle Scholar
  26. 26.
    Casas A, Battah S, Di Venosa G, Dobbin P, Rodriguez L, Fukuda H, Batlle A, MacRobert AJ (2009) Sustained and efficient porphyrin generation in vivo using dendrimer conjugates of 5-ALA for photodynamic therapy. J Control Release 135:136–143CrossRefGoogle Scholar
  27. 27.
    Al-Jamal KT, Al-Jamal WT, Wang JT, Rubio N, Buddle J, Gathercole D, Zloh M, Kostarelos K (2013) Cationic poly-l-lysine dendrimer complexes doxorubicin and delays tumor growth in vitro and in vivo. ACS Nano 7:1905–1917CrossRefGoogle Scholar
  28. 28.
    Kolhe P, Misra E, Kannan RM, Kannan S, Lieh-Lai M (2003) Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers. Int J Pharm 259:143–160CrossRefGoogle Scholar
  29. 29.
    Kirkpatrick GJ, Plumb JA, Sutcliffe OB, Flint DJ, Wheate NJ (2011) Evaluation of anionic half generation 3.5–6.5 poly(amidoamine) dendrimers as delivery vehicles for the active component of the anticancer drug cisplatin. J Inorg Biochem 105:1115–1122CrossRefGoogle Scholar
  30. 30.
    Wachter E, Dees C, Harkins J, Scott T, Petersen M, Rush RE, Cada A (2003) Topical rose bengal: preclinical evaluation of pharmacokinetics and safety. Lasers Surg Med 32:101–110CrossRefGoogle Scholar
  31. 31.
    Tardivo JP, Giglio AD, de Oliveira CS, Gabrielli DS, Junqueira HC, Tada DB, Severino D, de Fátima Turchiello R, Baptista MS (2005) Methylene blue in photodynamic therapy: from basic mechanisms to clinical applications. Photodiagn Photodyn Ther 2:175–191CrossRefGoogle Scholar
  32. 32.
    Xu D, Neckerst DC (1987) Aggregation of rose bengal molecules in solution. J Photochem Photobiol A 40:361–370CrossRefGoogle Scholar
  33. 33.
    Patil K, Pawar R, Talap P (2000) Self-aggregation of methylene blue in aqueous medium and aqueous solutions of Bu4NBr and urea. Phys Chem Chem Phys 2:4313–4317CrossRefGoogle Scholar
  34. 34.
    Dabrzalska M, Zablocka M, Mignani S, Majoral JP, Klajnert-Maculewicz B (2015) Phosphorous dendrimers and photodynamic therapy. Spectroscopic studies on two dendrimer on two dendrimer-photosensitizer complexes: cationic phosphorus dendrimer with rose bengal and anionic phosphorus dendrimer with methylene blue. Int J Pharm 492:266–274CrossRefGoogle Scholar
  35. 35.
    Barnadas-Rodríguez R, Cladera J (2015) Steroidal surfactants: detection of premicellar aggregation, secondary aggregation changes in micelles, and hosting of a highly charged negative substrate. Langmuir 31:8980–8988CrossRefGoogle Scholar
  36. 36.
    Dong A, Huang P, Caughey WS (1990) Protein secondary structures in water from second-derivative amide I infrared spectra. Biochemistry 29:3303–3308CrossRefGoogle Scholar
  37. 37.
    Andre W, Sandt C, Dumas P, Djian P, Hoffner G (2013) Structure of inclusions of Huntington’s disease brain revealed by synchrotron infrared microspectroscopy: polymorphism and relevance to cytotoxicty. Anal Chem 85:3765–3773CrossRefGoogle Scholar
  38. 38.
    Hankare PP, Jadhav AV, Patil RP, Garadkar KM, Mulla IS, Sasikala R (2014) Photocatalytic degradation of rose bengal in visible light with Cr substituted MnFe2O4 ferrospinel. Arch Phys Res 3:269–276Google Scholar
  39. 39.
    Xiong L, Yang Y, Mai J, Sun W, Zhang C, Wei D, Chen Q, Ni J (2010) Adsorption behavior of methylene blue onto titanate nanotubes. Chem Eng J 156:313–320CrossRefGoogle Scholar
  40. 40.
    Szulc A, Zablocka M, Coppel Y, Bijani C, Dabkowski W, Bryszewska M, Klajnert-Maculewicz B, Majoral JP (2014) A viologen phosphorus dendritic molecule as a carrier of ATP and mant-ATP: spectrofluorimetric and NMR studies. New J Chem 38:6212–6622CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Monika Dabrzalska
    • 1
  • Nuria Benseny-Cases
    • 2
  • Ramon Barnadas-Rodríguez
    • 3
  • Serge Mignani
    • 4
  • Maria Zablocka
    • 5
  • Jean-Pierre Majoral
    • 6
    • 7
  • Maria Bryszewska
    • 1
  • Barbara Klajnert-Maculewicz
    • 1
    • 8
  • Josep Cladera
    • 3
    Email author
  1. 1.Department of General Biophysics, Faculty of Biology and Environmental ProtectionUniversity of LodzLodzPoland
  2. 2.ALBA SynchrotronCerdanyola del VallèsSpain
  3. 3.Biophysics Unit and Center of Studies in Biophysics, Department of Biochemistry and Molecular BiologyUniversitat Autònoma de BarcelonaBellaterraSpain
  4. 4.PRES Sorbonne Paris Cité, CNRS UMR 860, Laboratoire de Chimie et de Biochimie pharmacologiques et toxicologiqueUniversité Paris DescartesParisFrance
  5. 5.Centre of Molecular and Macromolecular StudiesPolish Academy of SciencesLodzPoland
  6. 6.Laboratoire de Chimie de Coordination CNRSToulouseFrance
  7. 7.Université de Toulouse, UPS, INPTToulouse Cedex 4France
  8. 8.Leibniz-Institut für Polymerforschung Dresden e.V.DresdenGermany

Personalised recommendations