Development of DNA polymer films as a drug delivery system for the treatment of oral cancer


DNA polymer films (DNA-PFs) hold promise for use in drug delivery systems (DDS). In this study, the growth pattern of oral squamous cell carcinoma (OSCC) cells was evaluated on DNA-PFs incorporated with a photoactive compound chlorine aluminum phthalocyanine (DNA-PFs-AlClPc) and the efficacy of DNA-PFs-AlClPc as a DDS for photodynamic therapy (PDT) for the treatment of mucosal cancer. Flow cytometry was used to evaluate cell viability following application of DNA-PFs-AlClPc during PDT; the results demonstrated a positive response to photo stimulation within the range of light doses used (300, 600, and 1200 mJ/cm2). Reduced viability and increased cell death were observed with increasing doses than in the controls. As expected, the viability was reduced by more than 30% at the highest dose (1200 mJ/cm2). Flow cytometry revealed that the main mechanism of cell death induction was apoptosis (early and late apoptosis). These results demonstrate the potential of applying DNA-PFs-AlClPc as a DDS for other active molecules in the treatment of other pathologies. Furthermore, this system allows other drugs to be associated with DNA-PFs, indicating the potential use of this nanostructure in novel ways for the treatment of different neoplasms, such as oral cancer. Additionally, DNA nanostructured films may be used to support cell growth and subsequently as a “curative material” incorporated with an active or photoactive compound that can induce tissue regeneration.


This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Data availability



  1. 1.

    Prince A, Aguirre-Ghizo J, Genden E, Posner M, Sikora A. Head and neck squamous cell carcinoma: new translational therapies. Mt Sinai J Med. 2010;77(6):684–99.

    PubMed  Google Scholar 

  2. 2.

    Rapidis AD, Wolf GT. Immunotherapy of head and neck cancer: current and future considerations. J Oncol. 2009;2009:1–11.

    Google Scholar 

  3. 3.

    Shtenberg Y, Goldfeder M, Prinz H, Shainsky J, Ghantous Y, El-Naaj IA, et al. Mucoadhesive alginate pastes with embedded liposomes for local oral drug delivery. Int J Biol Macromol. 2018;111:62–9.

    CAS  PubMed  Google Scholar 

  4. 4.

    Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013;31(36):4550–9.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Thanki K, Gangwal RP, Sangamwar AT, Jain S. Oral delivery of anticancer drugs: challenges and opportunities. J Control Release. 2013;170(1):15–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Rupakar P, Parmar M, Shah M. Oral cancer-a real threat to society. Int J Med Paediatr Oncol. 2016;2(1):33–9.

    Google Scholar 

  7. 7.

    Florea AM, Büsselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers. 2011;3(1):1351–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Fukushima T, Kawaguchi M, Hayakawa T, Takeda S, Inoue Y, Ohno J, et al. Drug binding and releasing characteristics of DNA/lipid/PLGA film. Dent Mater J. 2007;26(6):854–60.

    CAS  PubMed  Google Scholar 

  9. 9.

    Jeong H, Ranallo S, Rossetti M, Heo J, Shin J, Park K, et al. Electronic activation of a DNA nanodevice using a multilayer nanofilm. Small. 2016;12(40):5572–8.

    CAS  PubMed  Google Scholar 

  10. 10.

    Jayme CC, de Paula LB, Rezende N, Calori IR, Franchi LP, Tedesco AC. DNA polymeric films as a support for cell growth as a new material for regenerative medicine: compatibility and applicability. Exp Cell Res. 2017;360:404–12.

    CAS  PubMed  Google Scholar 

  11. 11.

    Jayme CC, Kanicki J, Kajzar FO, Nogueira AF, Pawlicka A. Influence of DNA and DNA-PEDOT: PSS on dye sensitized solar cell performance. Mol Cryst Liq Cryst. 2016;627(1):38–48.

    CAS  Google Scholar 

  12. 12.

    Shahabadi N, Mohammadi S, Alizadeh R. DNA interaction studies of a new platinum (II) complex containing different aromatic dinitrogen ligands. Bioinorg Chem Appl. 2011;2011.

  13. 13.

    Zhao YX, Shaw A, Zeng X, Benson E, Nystroêm AM, Hoegberg B. DNA origami delivery system for cancer therapy with tunable release properties. ACS Nano. 2012;6(10):8684–91.

    CAS  PubMed  Google Scholar 

  14. 14.

    Shah JP, Gil Z. Current concepts in management of oral cancer-surgery. Oral Oncol. 2009;45(4–5):394–401.

    PubMed  Google Scholar 

  15. 15.

    Ibbotson SH, Ferguson J. Ambulatory photodynamic therapy using low irradiance inorganic light emitting diodes for the treatment of non-melanoma skin cancer: an open study. Photodermatol Photoimmunol Photomed. 2012;28(5):235–9.

    PubMed  Google Scholar 

  16. 16.

    Szeimies R-M, Lischner S, Philipp Dormston W, Walker T, Hiepe Wegener D, Feise K, et al. Photodynamic therapy for skin rejuvenation: treatment options results of a consensus conference of an expert group for aesthetic photodynamic therapy. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2013;11(7):632–6.

    PubMed  Google Scholar 

  17. 17.

    Moore CM, Nathan TR, Lees WR, Mosse CA, Freeman A, Emberton M, et al. Photodynamic therapy using meso tetra hydroxy phenyl chlorin (mTHPC) in early prostate cancer. Lasers Surg Med. 2006;38(5):356–63.

    CAS  PubMed  Google Scholar 

  18. 18.

    Betrouni N, Lopes R, Puech P, Colin P, Mordon S. A model to estimate the outcome of prostate cancer photodynamic therapy with TOOKAD Soluble WST11. Phys Med Biol. 2011;56(15):4771–83.

    PubMed  Google Scholar 

  19. 19.

    Meisel P, Kocher T. Photodynamic therapy for periodontal diseases: state of the art. J Photochem Photobiol B Biol. 2005;79(2):159–70.

    CAS  Google Scholar 

  20. 20.

    Pellosi DS, Paula LB, de Melo MT, Tedesco AC. Targeted and synergic glioblastoma treatment: multifunctional nanoparticles delivering verteporfin as adjuvant therapy for temozolomide chemotherapy. Mol Pharm. 2019;16(3):1009–24.

    CAS  PubMed  Google Scholar 

  21. 21.

    Usol'tsevava NV, Smirnova AI, Kazak AV, Giricheva NI, Galanin NE, Shaposhnikov GP, et al. Mix-substituted phthalocyanines of a “push–pull”-type and their metal complexes as prospective nanostructured materials for optoelectronics. Opto-Electron Rev. 2017;25(2):127–36.

    Google Scholar 

  22. 22.

    Surin AM, Sharipov RR, KrasilΓÇÖnikova IA, Boyarkin DP, Lisina OY, Gorbacheva LR, et al. Disruption of functional activity of mitochondria during MTT assay of viability of cultured neurons. Biochem Mosc. 2017;82(6):737–49.

    CAS  Google Scholar 

  23. 23.

    Calori IR, Jayme CC, Ueno LT, Machado FBC, Tedesco AC. Theoretical and experimental studies concerning monomer/aggregates equilibrium of zinc phthalocyanine for future photodynamic action. Spectrochim Acta A Mol Biomol Spectrosc. 2019.

  24. 24.

    de Paula CS, Tedesco AC, Primo FL, Vilela JMC, Andrade MS, Mosqueira VCF. Chloroaluminium phthalocyanine polymeric nanoparticles as photosensitisers: Photophysical and physicochemical characterisation, release and phototoxicity in vitro. Eur J Pharm Sci. 2013;49(3):371–81.

    PubMed  Google Scholar 

  25. 25.

    Portilho FA, de Oliveira Cavalcanti CE, Miranda-Vilela AL, Estevanato LLC, Longo JPF, Santos MDFMA, et al. Antitumor activity of photodynamic therapy performed with nanospheres containing zinc-phthalocyanine. J Nanobiotechnol. 2013;11(1):41.

    Google Scholar 

  26. 26.

    Nunes SMT, Sguilla FS, Tedesco AC. Photophysical studies of zinc phthalocyanine and chloroaluminum phthalocyanine incorporated into liposomes in the presence of additives. Braz J Med Biol Res. 2004;37(2):273–84.

    CAS  PubMed  Google Scholar 

  27. 27.

    Tapajós ECC, Longo JP, Simioni AR, Lacava ZGM, Santos MFMA, Morais PC, et al. In vitro photodynamic therapy on human oral keratinocytes using chloroaluminum-phthalocyanine. Oral Oncol. 2008;44(11):1073–9.

    PubMed  Google Scholar 

  28. 28.

    Jayme CC, Calori IR, Tedesco AC. Spectroscopic analysis of aluminum chloride phthalocyanine in binary water/ethanol systems as a new drug delivery system for photodynamic therapy cancer treatment. Spectrochim Acta A Mol Biomol Spectrosc. 2015.

  29. 29.

    Jayme CC, Calori IR, Cunha EMF, Tedesco AC. Evaluation of aluminum phthalocyanine chloride and DNA interactions for the design of an advanced drug delivery system in photodynamic therapy. Spectrochim Acta A Mol Biomol Spectrosc. 2018;201:242–8.

    CAS  PubMed  Google Scholar 

  30. 30.

    Rezende N, Jayme CC, Brassesco MS, Tedesco AC, de Oliveira HF. Standardization of a resazurin-based assay for the evaluation of metabolic activity in oral squamous carcinoma and glioblastoma cells. Photodiagn Photodyn Ther. 2019;26:371–4.

    CAS  Google Scholar 

  31. 31.

    Bolfarini GC, Siqueira-Moura MP, Demets GJ, Tedesco AC. Preparation, characterization, and in vitro phototoxic effect of zinc phthalocyanine cucurbit [7] uril complex encapsulated into liposomes. Dyes Pigments. 2014;100:162–7.

    CAS  Google Scholar 

  32. 32.

    Siqueira-Moura MP, Primo FL, Espreafico EM, Tedesco AC. Development, characterization, and photocytotoxicity assessment on human melanoma of chloroaluminum phthalocyanine nanocapsules. Mater Sci Eng C. 2013;33(3):1744–52.

    CAS  Google Scholar 

  33. 33.

    Ueno LT, Jayme CC, Silva LR, Pereira EB, Oliveira SM, Machado AE. Photophysics and spectroscopic properties of zinc phthalocyanine revisited using quantum chemistry. J Braz Chem Soc. 2012;23(12):2237–47.

    CAS  Google Scholar 

  34. 34.

    Eaton D. International union of pure and applied chemistry organic chemistry division commission on photochemistry: reference materials for fluorescence measurement. J Photochem Photobiol B Biol. 1988;2(4):523–31.

    CAS  Google Scholar 

  35. 35.

    Crosby GA, Demas JN. Measurement of photoluminescence quantum yields. Review. J Phys Chem. 1971;75(8):991–1024.

    CAS  Google Scholar 

  36. 36.

    Oliveira D, Macaroff P, Ribeiro K, Lacava Z, Azevedo R, Lima E, et al. Studies of zinc phthalocyanine/magnetic fluid complex as a bifunctional agent for cancer treatment. J Magn Magn Mater. 2005;289:476–9.

    CAS  Google Scholar 

  37. 37.

    Sibata M, Tedesco AC, Marchetti JM. Photophysicals and photochemicals studies of zinc (II) phthalocyanine in long time circulation micelles for photodynamic therapy use. Eur J Pharm Sci. 2004;23(2):131–8.

    CAS  PubMed  Google Scholar 

  38. 38.

    Ferreira SC, Bruns RE, Ferreira HS, Matos GD, David JM, Brandao GC, et al. Box-Behnken design: an alternative for the optimization of analytical methods. Anal Chim Acta. 2007;597(2):179–86.

    CAS  PubMed  Google Scholar 

  39. 39.

    de Oliveira FS, Korn M. Spectrophotometric determination of sulphate in automotive fuel ethanol by sequential injection analysis using dimethylsulphonazo (III) reaction. Talanta. 2006;68(3):992–9.

    PubMed  Google Scholar 

  40. 40.

    Grote JG, Diggs DE, Nelson RL, Zetts JS, Hopkins FK, Ogata N, et al. DNA photonics [deoxyribonucleic acid]. Mol Cryst Liq Cryst. 2005;426(1):3–17.

    CAS  Google Scholar 

  41. 41.

    Wang L, Yoshida J, Ogata N, Sasaki S, Kajiyama T. Self-assembled supramolecular films derived from marine deoxyribonucleic acid (DNA)− cationic surfactant complexes: large-scale preparation and optical and thermal properties. Chem Mater. 2001;13(4):1273–81.

    CAS  Google Scholar 

  42. 42.

    Marasini N, Yan YD, Poudel BK, Choi HG, Yong CS, Kim JO. Development and optimization of self-nanoemulsifying drug delivery system with enhanced bioavailability by Box–Behnken design and desirability function. J Pharm Sci. 2012;101(12):4584–96.

    CAS  PubMed  Google Scholar 

  43. 43.

    Rapolu K, Sanka K, Vemula PK, Aatipamula V, Mohd AB, Diwan PV. Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design. Drug Dev Ind Pharm. 2013;39(12):1928–35.

    CAS  PubMed  Google Scholar 

  44. 44.

    Ranch KM, Maulvi FA, Naik MJ, Koli AR, Parikh RK, Shah DO. Optimization of a novel in situ gel for sustained ocular drug delivery using Box-Behnken design: in vitro, ex vivo, in vivo and human studies. Int J Pharm. 2019;554:264–75.

    CAS  PubMed  Google Scholar 

  45. 45.

    Barros Neto B, Scarminio IS, Bruns RE. Como fazer experimentos: pesquisa e desenvolvimento na ciência e na industria: Editora da UNICAMP; 2003.

  46. 46.

    Slepička P, Kasálková NS, Stránská E, Bačáková L, Švorčík V. Surface characterization of plasma treated polymers for applications as biocompatible carriers. Express Polym Lett. 2013;7(6).

  47. 47.

    Bajpai AK, Bhatt R, Katare R. Atomic force microscopy enabled roughness analysis of nanostructured poly (diaminonaphthalene) doped poly (vinyl alcohol) conducting polymer thin films. Micron. 2016;90:12–7.

    CAS  PubMed  Google Scholar 

  48. 48.

    Martin JY, Schwartz Z, Hummert TW, Schraub DM, Simpson J, Lankford J, et al. Effect of titanium surface roughness on proliferation, differentiation, and protein synthesis of human osteoblast-like cells (MG63). J Biomed Mater Res A. 1995;29(3):389–401.

    CAS  Google Scholar 

  49. 49.

    Gittens RA, McLachlan T, Olivares-Navarrete R, Cai Y, Berner S, Tannenbaum R, et al. The effects of combined micron-/submicron-scale surface roughness and nanoscale features on cell proliferation and differentiation. Biomaterials. 2011;32(13):3395–403.

    CAS  PubMed  Google Scholar 

  50. 50.

    Velasco-Ortega E, Monsalve-Guil L, España-López A, Jiménez-Guerra A, Garzón L, Alaminos M, et al. Relevant aspects in the surface properties in titanium dental implants for the cellular viability. Mater Sci Eng C. 2016;64:1–10.

    CAS  Google Scholar 

  51. 51.

    Umeda H, Mano T, Harada K, Tarannum F, Ueyama Y. Appearance of cell-adhesion factor in osteoblast proliferation and differentiation of apatite coating titanium by blast coating method. J Mater Sci Mater Med. 2017;28(8):112.

    PubMed  Google Scholar 

  52. 52.

    Andrukhov O, Huber R, Shi B, Berner S, Rausch-Fan X, Moritz A, et al. Proliferation, behavior, and differentiation of osteoblasts on surfaces of different microroughness. Dent Mater. 2016;32(11):1374–84.

    CAS  PubMed  Google Scholar 

  53. 53.

    Kahn JS, Hu Y, Willner I. Stimuli-responsive DNA-based hydrogels: from basic principles to applications. Acc Chem Res. 2017;50(4):680–90.

    CAS  PubMed  Google Scholar 

  54. 54.

    Slator C, Molphy Z, McKee V, Long C, Brown T, Kellett A. Di-copper metallodrugs promote NCI-60 chemotherapy via singlet oxygen and superoxide production with tandem TA/TA and AT/AT oligonucleotide discrimination. Nucleic Acids Res. 2018;46(6):2733–50.

    PubMed  PubMed Central  Google Scholar 

  55. 55.

    Upanan S, Yodkeeree S, Thippraphan P, Punfa W, Wongpoomchai R. The proanthocyanidin-rich fraction obtained from red rice germ and bran extract induces HepG2 hepatocellular carcinoma cell apoptosis. Molecules. 2019;24(4):813.

    PubMed Central  Google Scholar 

  56. 56.

    Murabayashi D, Mochizuki M, Tamaki Y, Nakahara T. Practical methods for handling human periodontal ligament stem cells in serum-free and serum-containing culture conditions under hypoxia: implications for regenerative medicine. Hum Cell. 2017;30(3):169–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Mochizuki M, Nakahara T. Establishment of xenogeneic serum-free culture methods for handling human dental pulp stem cells using clinically oriented in-vitro and in-vivo conditions. Stem Cell Res Ther. 2018;9(1):25.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Code availability



A.C.T. received financial support from the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES), the State of São Paulo Research Foundation (FAPESP) Thematic project # 2013/50181-1 & Project FINEP 01.10.0758.01, the National Council for Scientific and Technological Development (CNPq), and Project PRONON-SIPAR # 25000.077093/2015-86. C.C.J. received financial support from FAPESP Post-Doc projects #2018/10237-1, PNPD-USP-RP-Pharmaceutical Sciences, and CAPES (Ph.D. project). The National Institute of Science and Technology (INCT) of Nanobiotechnology project 573880/2008-5 also provided financial support.

Author information



Corresponding author

Correspondence to Antonio Claudio Tedesco.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ceron Jayme, C., Ferreira Pires, A. & Tedesco, A.C. Development of DNA polymer films as a drug delivery system for the treatment of oral cancer. Drug Deliv. and Transl. Res. (2020).

Download citation


  • DNA polymeric films
  • Photodynamic therapy
  • Drug delivery system
  • Oral cancer