Skip to main content

Advertisement

SpringerLink
Log in

A novel strategy for glioblastoma treatment combining alpha-cyano-4-hydroxycinnamic acid with cetuximab using nanotechnology-based delivery systems

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Combination therapy that uses multiple drugs against different molecular targets should be considered as interesting alternatives for treating complex diseases such as glioblastoma (GBM). Drugs like alpha-cyano-4-hydroxycinnamic acid (CHC) and the monoclonal antibody cetuximab (CTX) are already explored for their capacity to act against different hallmarks of cancer. Previous reports suggest that the simultaneous use of these drugs, as a novel combining approach, might result in additive or synergistic effects. Therefore, advances in nanotechnology-based delivery systems will inevitably bring nano-mediated therapeutic gains to the proposed combination since they enable the association of different drugs into a single carrier. The current study provides indications that the new dual therapeutic strategy proposed, in association with nanotechnology, provides significative improvements when compared to the use of isolated drugs. Nanotechnological tools were employed by developing polymeric nanoparticles based on poly(lactic-co-glycolic acid) and chitosan for CHC encapsulation. Furthermore, these structures were conjugated with CTX by supramolecular forces. In summary, the encapsulation of the CHC drug into the nanoparticles increased its individual therapeutic capacity. In addition, conjugation with CTX seemed to enhance therapeutic efficacy, especially for U251 GBM cells. In conclusion, developed nanostructured delivery systems exhibited a set of favorable attributes and potential to be applied as a promising new alternative for GBM treatment.

.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Ostrom QT, Gittleman H, Liao P, Vecchione-Koval T, Wolinsky Y, Kruchko C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2010–2014. Neuro-Oncology. 2017;19:v1–v88. https://doi.org/10.1093/neuonc/nox158.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lapointe S, Perry A, Butowski NA. Primary brain tumours in adults. Lancet. 2018;392:432–46. https://doi.org/10.1016/S0140-6736(18)30990-5.

    Article  PubMed  Google Scholar 

  3. Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev. 2001;15:1311–33. https://doi.org/10.1101/gad.891601.

    Article  CAS  PubMed  Google Scholar 

  4. Hekmatara T, Bernreuther C, Khalansky A, Theisen A, Weissenberger J, Matschke J, et al. Efficient systemic therapy of rat glioblastoma by nanoparticle-bound doxorubicin is due to antiangiogenic effects. Clin Neuropathol. 2009;28:153–64. https://doi.org/10.5414/NPP28153.

    Article  CAS  PubMed  Google Scholar 

  5. Veliz I, Loo Y, Castillo O, Karachaliou N, Nigro O, Rosell R. Advances and challenges in the molecular biology and treatment of glioblastoma—is there any hope for the future? Ann Transl Med. 2015;3:7. https://doi.org/10.3978/j.issn.2305-5839.2014.10.06.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Karsy M, Yoon N, Boettcher L, Jensen R, Shah L, MacDonald J, et al. Surgical treatment of glioblastoma in the elderly: the impact of complications. Neuro-Oncol. 2018;138:123–32. https://doi.org/10.1007/s11060-018-2777-9.

    Article  Google Scholar 

  7. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. https://doi.org/10.1016/j.cell.2011.02.013.

    Article  CAS  PubMed  Google Scholar 

  8. Agnihotri S, Zadeh G. Metabolic reprogramming in glioblastoma: the influence of cancer metabolism on epigenetics and unanswered questions. Neuro-oncol. 2015;18:160–72. https://doi.org/10.1093/neuonc/nov125.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Keller S, Schmidt MHH. EGFR and EGFRvIII promote angiogenesis and cell invasion in glioblastoma: combination therapies for an effective treatment. Int J Mol Sci. 2017;18:1295–314. https://doi.org/10.3390/ijms18061295.

    Article  CAS  PubMed Central  Google Scholar 

  10. Miranda-Goncalves V, Granja S, Martinho O, Honavar M, Pojo M, Costa BM, et al. Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas. Oncotarget. 2016;7:46335–53. https://doi.org/10.18632/oncotarget.21761.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Taylor TE, Furnari FB, Cavenee WK. Targeting EGFR for treatment of glioblastoma: molecular basis to overcome resistance. Curr Cancer Drug Targets. 2012;12:197–209. https://doi.org/10.2174/156800912799277557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bannister TD. Inhibitors of lactate transport: a promising approach in cancer drug discovery. In: Reference module in biomedical sciences; Encyclopedia of cancer. 3ed ed; 2019. p. 266–78. https://doi.org/10.1016/B978-0-12-801238-3.64996-6.

    Chapter  Google Scholar 

  13. Miranda-Gonçalves V, Reis RM, Baltazar F. Lactate transporters and pH regulation: potential therapeutic targets in glioblastomas. Curr Cancer Drug Targets. 2016;16:388–99. https://doi.org/10.2174/1568009616666151222150543.

    Article  CAS  PubMed  Google Scholar 

  14. Caruso JP, Koch BJ, Benson PD, Varughese E, Monterey MD, Lee AE, et al. pH, lactate, and hypoxia: reciprocity in regulating high-affinity monocarboxylate transporter expression in glioblastoma. Neoplasia. 2017;19:121–34. https://doi.org/10.1016/j.neo.2016.12.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Zahonero C, Sanchez-Gomez P. EGFR-dependent mechanisms in glioblastoma: towards a better therapeutic strategy. Cell Mol Life Sci. 2014;7:3465–88. https://doi.org/10.1007/s00018-014-1608-1.

    Article  CAS  Google Scholar 

  16. Hicks MJ, Chiuchiolo MJ, Ballon D, Dyke JP, Aronowitz E, Funato K, et al. Anti-epidermal growth factor receptor gene therapy for glioblastoma. PLoS One. 2016;11:e0162978. https://doi.org/10.1371/journal.pone.0162978.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zorzan M, Giordan E, Redaelli M, Caretta A, Mucignat-Caretta C. Molecular targets in glioblastoma. Future Oncol. 2015;11(9):1407–20. https://doi.org/10.2217/fon.15.22.

    Article  CAS  PubMed  Google Scholar 

  18. Binder ZA, Thorne AH, Bakas S, Wileyto EP, Bilello M, Akbari H, et al. Epidermal growth factor receptor extracellular domain mutations in glioblastoma present opportunities for clinical imaging and therapeutic development. Cancer Cell. 2018;34:163–77. e7. https://doi.org/10.1016/j.ccell.2018.06.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bax DA, Gaspar N, Little SE, Marshall L, Perryman L, Regairaz M, et al. EGFRvIII deletion mutations in pediatric high-grade glioma and response to targeted therapy in pediatric glioma cell lines. Clin Cancer Res. 2009;15:5753–61. https://doi.org/10.1158/1078-0432.CCR-08-3210.

    Article  CAS  PubMed  Google Scholar 

  20. Viana-Pereira M, Lopes JM, Little S, Milanezi F, Basto D, Pardal F, et al. Analysis of EGFR overexpression, EGFR gene amplification and the EGFRvIII mutation in Portuguese high-grade gliomas. Anticancer Res. 2008;28:913–20.

    PubMed  Google Scholar 

  21. Fukai J, Nishio K, Itakura T, Koizumi F. Antitumor activity of cetuximab against malignant glioma cells overexpressing EGFR deletion mutant variant III. Cancer Sci. 2008;99:2062–9. https://doi.org/10.1111/j.1349-7006.2008.00945.x.

    Article  CAS  PubMed  Google Scholar 

  22. Vincenzi B, Schiavon G, Silletta M, Santini D, Tonini G. The biological properties of cetuximab. Crit Rev Oncol Hematol. 2008;68:93–106. https://doi.org/10.1016/j.critrevonc.2008.07.006.

    Article  PubMed  Google Scholar 

  23. Golay J, Introna M. Mechanism of action of therapeutic monoclonal antibodies: promises and pitfalls of in vitro and in vivo assays. Arch Biochem Biophys. 2012;526:146–53. https://doi.org/10.1016/j.abb.2012.02.011.

    Article  CAS  PubMed  Google Scholar 

  24. Yang W, Zheng Y, Xia Y, Ji H, Chen X, Guo F, et al. ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol. 2012;14:1295–304. https://doi.org/10.1038/ncb2629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ferreira LMB, Alonso JD, Kiill CP, Ferreira NN, Buzzá HH, Martins de Godoi DR, et al. Exploiting supramolecular interactions to produce bevacizumab-loaded nanoparticles for potential mucosal delivery. Eur Polym J. 2018;103:238–50. https://doi.org/10.1016/j.eurpolymj.2018.04.013.

    Article  CAS  Google Scholar 

  26. Tzeng SY, Green JJ. Therapeutic nanomedicine for brain cancer. Ther Deliv. 2013;4:687–704. https://doi.org/10.4155/tde.13.38.

    Article  CAS  PubMed  Google Scholar 

  27. Pourgholi F, Hajivalili M, Farhad JN, Kafil HS, Yousefi M. Nanoparticles: novel vehicles in treatment of glioblastoma. Biomed Pharmacother. 2016;77:98–107. https://doi.org/10.1016/j.biopha.2015.12.014.

    Article  CAS  PubMed  Google Scholar 

  28. Mujokoro B, Adabi M, Sadroddiny E, Adabi M, Khosravani M. Nano-structures mediated co-delivery of therapeutic agents for glioblastoma treatment: a review. Mater Sci Eng C. 2016;69:1092–102. https://doi.org/10.1016/j.msec.2016.07.080.

    Article  CAS  Google Scholar 

  29. Ferreira NN, Caetano BL, Boni FI, Sousa F, Magnani M, Sarmento B, et al. Alginate-based delivery systems for bevacizumab local therapy: in vitro structural features and release properties. J Pharm Sci. 2018;108:1559–68. https://doi.org/10.1016/j.xphs.2018.11.038.

    Article  CAS  PubMed  Google Scholar 

  30. Wen Z, Yan Z, Hu K, Pang Z, Cheng X, Guo L, et al. Odorranalectin-conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson’s disease following intranasal administration. J Control Release. 2011;151:131–8. https://doi.org/10.1016/j.jconrel.2011.02.022.

    Article  CAS  PubMed  Google Scholar 

  31. Kumar M, Pandey RS, Patra KC, Jain SK, Soni ML, Dangi JS, et al. Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery. Int J Biol Macromol. 2013;61:189–95. https://doi.org/10.1016/j.ijbiomac.2013.06.041.

    Article  CAS  PubMed  Google Scholar 

  32. Crowe TP, Greenlee MHW, Kanthasamy AG, Hsu WH. Mechanism of intranasal drug delivery directly to the brain. Life Sci. 2018;195:44–52. https://doi.org/10.1016/j.lfs.2017.12.025.

    Article  CAS  PubMed  Google Scholar 

  33. Genchi GG, Marino A, Tapeinos C, Ciofani G. Smart materials meet multifunctional biomedical devices: current and prospective implications for nanomedicine. Front Bioeng Biotech. 2017;5:80. https://doi.org/10.3389/fbioe.2017.00080.

    Article  Google Scholar 

  34. Yu S, Xu X, Feng J, Liu M, Hu K. Chitosan and chitosan coating nanoparticles for the treatment of brain disease. Int J Pharm. 2019;560:282–93. https://doi.org/10.1016/j.ijpharm.2019.02.012.

    Article  CAS  PubMed  Google Scholar 

  35. Bonaccorso A, Musumeci T, Serapide MF, Pellitteri R, Uchegbu IF, Puglisi G. Nose to brain delivery in rats: effect of surface charge of rhodamine B labeled nanocarriers on brain subregion localization. Colloid Surface B. 2017;154:297–306. https://doi.org/10.1016/j.colsurfb.2017.03.035.

    Article  CAS  Google Scholar 

  36. Sanna V, Roggio AM, Siliani S, Piccinini M, Marceddu S, Mariani A, et al. Development of novel cationic chitosan-and anionic alginate-coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol. Int J Nanomedicine. 2012;7:5501–16. https://doi.org/10.2147/IJN.S36684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Miranda-Goncalves V, Honavar M, Pinheiro C, Martinho O, Pires MM, Pinheiro C, et al. Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets. Neuro-oncology. 2013;15:172–88. https://doi.org/10.1093/neuonc/nos298.

    Article  CAS  PubMed  Google Scholar 

  38. Miranda-Goncalves V, Cardoso-Carneiro D, Valbom I, Cury FP, Silva VA, Granja S, et al. Metabolic alterations underlying bevacizumab therapy in glioblastoma cells. Oncotarget. 2017;8:103657–70. https://doi.org/10.18632/oncotarget.21761.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Martinho O, Silva-Oliveira R, Cury FP, Barbosa AM, Granja S, Evangelista AF, et al. HER family receptors are important theranostic biomarkers for cervical cancer: blocking glucose metabolism enhances the therapeutic effect of HER inhibitors. Theranostics. 2017;7:717–32. https://doi.org/10.7150/thno.17154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Silva-Oliveira RJ, Melendez M, Martinho O, Zanon MF, de Souza VL, Carvalho AL, et al. AKT can modulate the in vitro response of HNSCC cells to irreversible EGFR inhibitors. Oncotarget. 2017;8:53288–301. https://doi.org/10.18632/oncotarget.18395.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Park AK, Francis JM, Park WY, Park JO, Cho J. Constitutive asymmetric dimerization drives oncogenic activation of epidermal growth factor receptor carboxyl-terminal deletion mutants. Oncotarget. 2015;6:8839–50. https://doi.org/10.18632/oncotarget.3559.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Combs SE, Schulz-Ertner D, Roth W, Herold-Mende C, Debus J, Weber K-J. In vitro responsiveness of glioma cell lines to multimodality treatment with radiotherapy, temozolomide, and epidermal growth factor receptor inhibition with cetuximab. Int J Radiat Oncol Biol Phys. 2007;68:873–82. https://doi.org/10.1016/j.ijrobp.2007.03.002.

    Article  CAS  PubMed  Google Scholar 

  43. Samaridou E, Alonso MJ. Nose-to-brain peptide delivery—the potential of nanotechnology. Bioorg Med Chem. 2018;26:2888–905. https://doi.org/10.1016/j.bmc.2017.11.001.

    Article  CAS  PubMed  Google Scholar 

  44. Gao X, Wu B, Zhang Q, Chen J, Zhu J, Zhang W, et al. Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration. J Control Release. 2007;121:156–67. https://doi.org/10.1016/j.jconrel.2007.05.026.

    Article  CAS  PubMed  Google Scholar 

  45. Migliore MM, Vyas TK, Campbell RB, Amiji MM, Waszczak BL. Brain delivery of proteins by the intranasal route of administration: a comparison of cationic liposomes versus aqueous solution formulations. J Pharm Sci. 2010;99:1745–61. https://doi.org/10.1002/jps.21939.

    Article  CAS  PubMed  Google Scholar 

  46. Xia H, Gao X, Gu G, Liu Z, Zeng N, Hu Q, et al. Low molecular weight protamine-functionalized nanoparticles for drug delivery to the brain after intranasal administration. Biomaterials. 2011;32(36):9888–98. https://doi.org/10.1016/j.biomaterials.2011.09.004.

    Article  CAS  PubMed  Google Scholar 

  47. Mittal D, Ali A, Md S, Baboota S, Sahni JK, Ali J. Insights into direct nose to brain delivery: current status and future perspective. Drug Deliv. 2014;21:75–86. https://doi.org/10.3109/10717544.2013.838713.

    Article  CAS  PubMed  Google Scholar 

  48. Martínez Rivas CJ, Tarhini M, Badri W, Miladi K, Greige-Gerges H, Nazari QA, et al. Nanoprecipitation process: from encapsulation to drug delivery. Int J Pharm. 2017;532(1):66–81. https://doi.org/10.1016/j.ijpharm.2017.08.064.

    Article  CAS  PubMed  Google Scholar 

  49. Rao JP, Geckeler KE. Polymer nanoparticles: preparation techniques and size-control parameters. Prog Polym Sci. 2011;36:887–913. https://doi.org/10.1016/j.progpolymsci.2011.01.001.

    Article  CAS  Google Scholar 

  50. Gao H. Progress and perspectives on targeting nanoparticles for brain drug delivery. Acta Pharm Sin B. 2016;6:268–86. https://doi.org/10.1016/j.apsb.2016.05.013.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Badran MM, Mady MM, Ghannam MM, Shakeel F. Preparation and characterization of polymeric nanoparticles surface modified with chitosan for target treatment of colorectal cancer. Int J Biol Macromol. 2017;95:643–9. https://doi.org/10.1016/j.ijbiomac.2016.11.098.

    Article  CAS  PubMed  Google Scholar 

  52. Bilati U, Allémann E, Doelker E. Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur J Pharm Sci. 2005;24:67–75. https://doi.org/10.1016/j.ejps.2004.09.011.

    Article  CAS  PubMed  Google Scholar 

  53. Kaszuba M, Corbett J, Watson FM, Jones A. High-concentration zeta potential measurements using light-scattering techniques. Philos Trans Royal Soc A. 2010;368:4439–51. https://doi.org/10.1098/rsta.2010.0175.

    Article  CAS  Google Scholar 

  54. Bento D, Staats HF, Goncalves T, Borges O. Development of a novel adjuvanted nasal vaccine: C48/80 associated with chitosan nanoparticles as a path to enhance mucosal immunity. Eur J Pharm Biopharm. 2015;93:149–64. https://doi.org/10.1016/j.ejpb.2015.03.024.

    Article  CAS  PubMed  Google Scholar 

  55. Schatz C, Domard A, Viton C, Pichot C, Delair T. Versatile and efficient formation of colloids of biopolymer-based polyelectrolyte complexes. Biomacromolecules. 2004;5:1882–92. https://doi.org/10.1021/bm049786+.

    Article  CAS  PubMed  Google Scholar 

  56. Pinto Reis C, Neufeld RJ, Ribeiro AJ, Veiga F. Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomedicine. 2006;2:8–21. https://doi.org/10.1016/j.nano.2005.12.003.

    Article  CAS  Google Scholar 

  57. Barichello JM, Morishita M, Takayama K, Nagai T. Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method. Drug Dev Ind Pharm. 1999;25:471–6. https://doi.org/10.1081/DDC-100102197.

    Article  CAS  PubMed  Google Scholar 

  58. Bhattacharjee S. DLS and zeta potential—what they are and what they are not? J Control Release. 2016;235:337–51. https://doi.org/10.1016/j.jconrel.2016.06.017.

    Article  CAS  PubMed  Google Scholar 

  59. Vilaça N, Amorim R, Martinho O, Reis RM, Baltazar F, Fonseca AM, et al. Encapsulation of α-cyano-4-hydroxycinnamic acid into a NaY zeolite. J Mater Sci. 2011;46:7511–6. https://doi.org/10.1007/s10853-011-5722-2.

    Article  CAS  Google Scholar 

  60. Wang Y, Li P, Kong L. Chitosan-modified PLGA nanoparticles with versatile surface for improved drug delivery. AAPS PharmSciTech. 2013;14:585–92. https://doi.org/10.1208/s12249-013-9943-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Mourya V, Inamdar NN. Trimethyl chitosan and its applications in drug delivery. J Mater Sci Mater Med. 2009;20:1057–79. https://doi.org/10.1007/s10856-008-3659-z.

    Article  CAS  PubMed  Google Scholar 

  62. de Britto D, de Moura MR, Aouada FA, Mattoso LH, Assis OB. N, N, N-trimethyl chitosan nanoparticles as a vitamin carrier system. Food Hydrocoll. 2012;27:487–93. https://doi.org/10.1016/j.foodhyd.2011.09.002.

    Article  CAS  Google Scholar 

  63. Kang B-S, Choi J-S, Lee S-E, Lee J-K, Kim T-H, Jang WS, et al. Enhancing the in vitro anticancer activity of albendazole incorporated into chitosan-coated PLGA nanoparticles. Carbohydr Polym. 2017;159:39–47. https://doi.org/10.1016/j.carbpol.2016.12.009.

    Article  CAS  PubMed  Google Scholar 

  64. Schubert S, Delaney JT Jr, Schubert US. Nanoprecipitation and nanoformulation of polymers: from history to powerful possibilities beyond poly (lactic acid). Soft Matter. 2011;7:1581–8. https://doi.org/10.1039/c0sm00862a.

    Article  CAS  Google Scholar 

  65. Vu-Quang H, Vinding MS, Xia D, Nielsen T, Ullisch MG, Dong M, et al. Chitosan-coated poly (lactic-co-glycolic acid) perfluorooctyl bromide nanoparticles for cell labeling in 19F magnetic resonance imaging. Carbohydr Polym. 2016;136:936–44. https://doi.org/10.1016/j.carbpol.2015.09.076.

    Article  CAS  PubMed  Google Scholar 

  66. Manjappa AS, Chaudhari KR, Venkataraju MP, Dantuluri P, Nanda B, Sidda C, et al. Antibody derivatization and conjugation strategies: application in preparation of stealth immunoliposome to target chemotherapeutics to tumor. J Control Release. 2011;150:2–22. https://doi.org/10.1016/j.jconrel.2010.11.002.

    Article  CAS  PubMed  Google Scholar 

  67. Nel AE, Madler L, Velegol D, Xia T, Hoek EMV, Somasundaran P, et al. Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater. 2009;8:543–57. https://doi.org/10.1038/nmat2442.

    Article  CAS  PubMed  Google Scholar 

  68. Ferreira NN, Ferreira LMB, Miranda-Gonçalves V, Reis RM, Seraphim TV, Borges JC, et al. Alginate hydrogel improves anti-angiogenic bevacizumab activity in cancer therapy. Eur J Pharm Biopharm. 2017;119:271–82. https://doi.org/10.1016/j.ejpb.2017.06.028.

    Article  CAS  PubMed  Google Scholar 

  69. Naahidi S, Jafari M, Edalat F, Raymond K, Khademhosseini A, Chen P. Biocompatibility of engineered nanoparticles for drug delivery. J Control Release. 2013;166(2):182–94. https://doi.org/10.1016/j.jconrel.2012.12.013.

    Article  CAS  PubMed  Google Scholar 

  70. Amorim R, Vilaça N, Martinho O, Reis RM, Sardo M, Rocha J, et al. Zeolite structures loading with an anticancer compound as drug delivery systems. J Phys Chem C. 2012;116:25642–50. https://doi.org/10.1021/jp3093868.

    Article  CAS  Google Scholar 

  71. Halestrap AP, Denton RM. Specific inhibition of pyruvate transport in rat liver mitochondria and human erythrocytes by alpha-cyano-4-hydroxycinnamate. Biochem J. 1974;138:313–6. https://doi.org/10.1042/bj1380313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the National Institute of Science and Technology in Pharmaceutical Nanotechnology: a transdisciplinary approach INCT-NANOFARMA, which is supported by the “Fundação de Amparo e Pesquisa do Estado de São Paulo” (FAPESP, Brazil), grant no. 2014/50928-2, and by “Conselho Nacional de Desenvolvimento Científico e Tecnológico” (CNPq, Brazil), grant no. 465687/2014-8.

Funding

This work was financially supported by Fundação de Amparo e Pesquisa do Estado de São Paulo (FAPESP), grant nos. 2017/16324-0, 2016/09671-3, and 2018/04546-1. SG received a fellowship from FCT, ref. SFRH/BPD/117858/2016. This work was also developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER), and through the Competitiveness Factors Operational Programme (COMPETE) and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038.

Author information

Authors and Affiliations

  1. School of Pharmaceutical Sciences, São Paulo State University, UNESP, Rodovia Araraquara/Jaú Km 1, Araraquara, São Paulo, 14801-902, Brazil

    Natália N. Ferreira, Fernanda Isadora Boni, Leonardo M. B. Ferreira & Maria Palmira D. Gremião

  2. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal

    Sara Granja, Rui M. Reis & Fátima Baltazar

  3. ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Sara Granja, Rui M. Reis & Fátima Baltazar

  4. Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo, Brazil

    Rui M. Reis

Authors
  1. Natália N. Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Granja
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fernanda Isadora Boni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Leonardo M. B. Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rui M. Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fátima Baltazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maria Palmira D. Gremião
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, methodology, and data acquisition: N.N.F.; S.G.; F.I.B.; L.M.B.F.; resources: M.P.D.G.; F.B.; R.M.R.; data curation: all authors; writing of original draft: N.N.F; writing-review and editing: all authors; supervision: M.P.D.G.; F.B.; R.M.R.; project administration and funding acquisition: N.N.F; M.P.D.G.; F.B.; R.M.R.; data analysis and scientific discussion: all authors

Corresponding author

Correspondence to Maria Palmira D. Gremião.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ferreira, N.N., Granja, S., Boni, F.I. et al. A novel strategy for glioblastoma treatment combining alpha-cyano-4-hydroxycinnamic acid with cetuximab using nanotechnology-based delivery systems. Drug Deliv. and Transl. Res. 10, 594–609 (2020). https://doi.org/10.1007/s13346-020-00713-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-020-00713-8

Keywords

Search

Navigation