Controlled release of targeted chemotherapeutic drug dabrafenib for melanoma cancers monitored using surface-enhanced Raman scattering (SERS) spectroscopy

Authors

  • Logan Running SUNY Potsdam
  • Ricardo Espinal SUNY Potsdam
  • Maria Hepel SUNY Potsdam

DOI:

https://doi.org/10.13171/mjc71/01803171500-hepel

Abstract

The advanced skin cancer melanoma, which is primarily caused by the mutation of BRAF gene, has a high mortality rate and requires high doses of chemotherapeutic drugs. To mitigate the drug toxicity to healthy cells and other side effects, the development of alternative modes of treatment has been extensively sought after. Herein, we describe a new targeted drug delivery system with controlled release, based on nanoparticle nanocarriers functionalized with folate and transferrin ligands for recognition of the respective receptors overexpressed in cancer cell membrane. We have investigated the immobilization of a new drug dabrafenib onto the nanocarriers and its controlled release, aided with surface-enhanced Raman scattering (SERS) spectroscopy which affords ultra-sensitive in situ measurement ability owing to the high signal amplification, associated with strong plasmonic fields of the nanocarrier gold nanoparticle (AuNP) cores. The nanocarriers were equipped with Raman reporters: mercaptobenzoic acid (MBA) and para-aminothiophenol (PATP) forming a mixed thiolate monolayer shell on AuNPs. The dabrafenib was covalently attached to MBA via an amide bond which is pH sensitive and enables the drug release at lower pH encountered in cancer cells. This arrangement in the drug binding to the nanocarrier protects the dabrafenib amine group against deactivation until the drug release in the target tumor cells.

Author Biographies

Logan Running, SUNY Potsdam

Department of Chemistrystudent

Ricardo Espinal, SUNY Potsdam

Department of Chemistrystudent

Maria Hepel, SUNY Potsdam

Department of Chemistry,Distinguished Professor

References

- A.H. Shain and B.C. Bastian, Nat. Rev. Cancer, 2016, 16, 345-358.

- G.V. Long and e. al., J. Clin. Oncol., 2011, 29, 1239-1246.

- J. Shi, P.W. Kantoff, R. Wooster and O.C. Farokhzad, Nat. Rev. Cancer, 2017, 17, 20-37.

- M. Smith and M. Hepel, Mediterr. J. Chem., 2017, 6, 125-132.

- T. Santiago, R.S. DeVaux, K. Kurzatkowska, R. Espinal, J.I. Herschkowitz and M. Hepel, Int. J. Nanomed., 2017, 12, 7763-7776.

- K. Kurzatkowska, T. Santiago and M. Hepel, Biosens. Bioelectron., 2017, 91, 780-787.

- H. Ilkhani, T. Hughes, J. Li, C.J. Zhong and M. Hepel, Biosens. Bioelectron., 2016, 80, 257-264.

- A.M. Menzies, G.V. Long and R. Murali, Drug Des. Devel. Ther., 2012, 6, 391-405.

- S. Horn and et al., Science, 2013, 339, 959-961.

- F.W. Huang and et al., Science, 2013, 957-959.

- J.J. Grob, M.M. Amonkar, B. Karaszewska, J. Schachter, R. Dummer, A. Mackiewicz, D. Stroyakovskiy, K. Drucis, F. Grange, V. Chiarion-Sileni, P. Rutkowski, M. Lichinitser, et al., Lancet Oncol., 2015, 16, 1389-1398.

- L. Spain, M.J. M and J. Larkin, Expert Opin. Pharmacother., 2016, 17, 1031-1038.

- M. Schreuer, Y. Jansen, S. Planken, I. Chevolet, T. Seremet, V. Kruse and B. Neyns, Lancet Oncol., 2017, 18, 464-472.

- US National Library of Medicine. ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01052142?term.

- Y.T. Ko, C. Falcao and V.P. Torchilin, Mol. Pharm., 2009, 6, 971-977.

- Y.F. Zhang, J.C. Wang, D.Y. Bian, X. Zhang and Q. Zhang, Eur. J. Pharm. Biopharm., 2010, 74, 467-473.

- S. Sengupta and et al., Nature, 2005, 436, 568-572.

- J. Park and et al., Nat. Mater., 2012, 11, 895-905.

- A.A. Mouineer, A.F. Zaher, A.A. El-malah and E.A.e.-f. Sobh, Mediterr. J. Chem., 2017, 6, 165-179.

- J. Li, Z. Skeete, S. Shan, S. Yan, K. Kurzatkowska, W. Zhao, Q.M. Ngo, P. Holubovska, J. Luo, M. Hepel and C.J. Zhong, Anal. Chem., 2015, 87, 10698-10702.

- A. Hulikova, A.L. Harris, R.D. Vaughan-Jones and P. Swietach, J. Cell Physiol., 2013, 228, 743-752.

- Y. Kato, S. Ozawa, C. Miyamoto, Y. Maehata, A. Suzuki, T. Maeda and Y. Baba, Cancer Cell International, 2013, 13, 89.81-88.

- P. Swietach, R.D. Vaughan-Jones, A.L. Harris and A. Hulikova, Phil. Trans. R. Soc. B, 2014, 369, 20130099.

- J. Sudimack and R.J. Lee, Adv. Drug Deliv. Rev., 2000, 41, 147-162.

- R.C. Lynn, M. Poussin, A. Kalota, Y. Feng, P.S. Low, D.S. Dimitrov and D.J. Powell, Blood, 2015, 125, 3466-3476.

- D.R. Richardson, D.S. Kalinowski, S. Lau, P.J. Jansson and D.B. Lovejoy, Biochim. Biophys. Acta, 2009, 1790, 702-717.

- K. Ho, H. Li, Z. Qian and H. Sun, Pharm. Rev., 2002, 54, 561-587.

- J.J. Turek, C.P. Leamon and P.S. Low, J. Cell. Sci., 1993, 106, 423-430.

- Y. Lu and P.S. Low, Adv. Drug Deliv. Rev., 2002, 54, 675-693.

- M. Hepel and M. Stobiecka, J. Photochem. Photobiol. A, 2011, 225, 72-80.

- D.R. Richardson and P. Ponka, Biochim. Biophys. Acta, 1997, 1331, 1-40.

- E. Ryschich, G. Huszty, H.P. Knaebel, M. Hartel, M.W. Buchler and J. Schmidt, Eur. J. Cancer, 2004, 40, 1418-1422.

- M.R. Girotti and R. Marais, Cancer Discov., 2013, 3, 487-490.

- J.G. Samaritoni, A.T. Copes, D.K. Crews, C. Glos, A.L. Thompson, C. Wilson, M.J. O'Donnell and W.L. Scott, J. Org. Chem., 2014, 79, 3140-3151.

- M. Szostak, L. Yao and J. Aubé, J. Org. Chem., 2009, 74, 1869-1875.

- B.M. Brandsen, A.R. Hesser, M.A. Castner, M. Chandra and S.K. Silverman, J. Am. Chem. Soc., 2013, 135, 16014-16017.

- C. Zhou, J.L. Avins, P.C. Klauser, B.M. Brandsen, Y. Lee and S.K. Silverman, J. Am. Chem. Soc., 2016, 138, 2106-2109.

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Published

2018-03-17

Issue

Section

Nanochemistry