Spectral Analysis of Nanodiamond-Berberine Complex Interaction with Living Cells for Nanoparticle Mediated Drug Delivery

Yu-Chung Lin
Department of Physics, National Dong Hwa University, Hualien, Taiwan
Institute of Physics, Academia Sinica, Taipei, Taiwan

Zhe-Rui Lin
Department of Physics, National Dong Hwa University, Hualien, Taiwan

Lin-Wei Tsai
Department of Physics, National Dong Hwa University, Hualien, Taiwan

Elena Perevedentseva
Department of Physics, National Dong Hwa University, Hualien, Taiwan
P. N. Lebedev Physics Institute of Russian Academy of Science, Moscow, Russia

Artashes Karmenyan
Department of Physics, National Dong Hwa University, Hualien, Taiwan

Chia-Liang Cheng (Login required)
Department of Physics, National Dong Hwa University, Hualien, Taiwan

Paper #3162 received 27 Feb 2017; revised manuscript received 17 Apr 2017; accepted for publication 19 Apr 2017; published online 30 Apr 2017.

DOI: 10.18287/JBPE17.03.010305


The natural isoquinoline alkaloid berberine has been demonstrated for its significant activity against a variety of deceases caused by bacterial and parasite infections. Nanodiamond (ND) has also been proven to have great potential for drug delivery. In this work, the complex of ND with berberine is constructed through surface functionalized ND, aiming for drug delivery applications. Spectroscopic analysis was performed on the complex interaction with human lung alveolar carcinoma epithelial cell (A549) and red blood cell (RBC) in comparison with berberine in solution. The studied cells were treated with carboxylated ND, ND-berberine complex and berberine, respectively. Their distributions in cells structures are visualized using ND and berberine’s fluorescence signals for detection. The distribution of ND and ND-berberine complex differs with the distribution of berberine introduced in solution form. The results show that the ND with attached drug molecules can act as a drug carrier allowing controllable localization of the drug into the cell. This result can have implication in drug delivery, release and delivery tracing applications.


Nanodiamond; Berberine; Bio-Applications; Medical Applications; Fluorescence; Surface Functionality; Imaging; Drug delivery; Nanobiotechnology

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1. D. Ho (ed.), Nanodiamonds: Applications in Biology and Nanoscale Medicine, Springer Science & Business Media, New York (2009). ISBN: 978-1-4419-0530-7.

2. E. Perevedentseva, Y.-C. Lin, M. Jani, and C.-L. Cheng, “Biomedical Applications of Nanodiamond in Imaging and Therapy,” Future Medicine. Nanomedicine 8(12), 2041-2060 (2013). Crossref

3. J. Walker, “Optical absorption and luminescence in diamond,” Rep. Prog. Phys. 42, 1605-1659 (1979).

4. V. N. Mochalin, O. Shenderova, D. Ho, and Yu. Gogotsi, “The Properties and Applications of Nanodiamonds,” Nat. Nanotechnol. 7, 11-23 (2012).

5. Y. Y. Hui, C. L. Cheng, and H. C. Chang, “Nanodiamonds for optical bioimaging,” J. Phys. D Appl. Phys. 43(37), 374021 (2010). Crossref

6. A. Krueger, and D. Lang, “Functionality is key: recent progress in the surface modification of nanodiamond,” Adv. Funct. Mater. 22(5), 890-906 (2012).

7. O. A. Shenderova, and G. E. McGuire, “Science and engineering of nanodiamond particle surfaces for biological applications (Review),” Biointerphases 10(3), 030802 (2015).

8. E. Osawa, and D. Ho, “Nanodiamond and its application to drug delivery,” J. Med. Allied Sci. 2(2), 31-40 (2012).

9. K.M. El-Say, “Nanodiamond as a drug delivery system: applications and prospective,” J. Appl. Pharm. Sci. 01(06), 29-39 (2011).

10. R. Kaur, and I. Badea, “Nanodiamonds as novel nanomaterial for biomedical applications: drug delivery and imaging systems,” Int. J. Nanomedicine 8, 203-220 (2013).

11. E. Perevedentseva, P.-J. Cai, Y.-C. Chiu, and C.-L. Cheng, “Characterizing protein activities of lysozyme and nanodiamond complex prepared for bio applications,” Langmuir 27(3), 1085-1091 (2011). Crossref

12. Y. Kuo, T.-Y. Hsu, Y.-C. Wu, and H.-C. Chang, “Fluorescent nanodiamond as a probe for the intercellular transport of proteins in vivo,” Biomaterials 34(33), 8352–836 (2013). Crossref

13. O. Faklaris, V. Joshi, T. Irinopoulou, P. Tauc, M. Sennour, H. Girard, C. Gesset, J.-C. Arnault, A. Thorel, J.-P. Boudou, P. A. Curmi, and F. Treussart, “Photoluminescent Diamond Nanoparticles for Cell Labeling: Study of the Uptake Mechanism in Mammalian Cells,” ACS Nano, 3(12), 3955-3962 (2009).

14. K.-J. Huang, C.-Y. Lee, Y.-C. Lin, C.-Y. Lin, E. Perevedentseva, S.-F. Hung, and C.-L. Cheng, “Phagocytosis and immune response studies of Macrophage-Nanodiamond Interactions in vitro and in vivo,” J. Biophotonics, Jan (2017).

15. Z. Chu, S. Zhang, B. Zhang, C. Zhang, C.-Y. Fang, I. Rehor, P. Cigler, H.-C. Chang, G. Lin, R. Liu, and Q. Li, “Unambiguous observation of shape effects on cellular fate of nanoparticles,” Scientific Reports 4, 4495 (2014).

16. Y.-C. Lin, L.-W. Tsai, E. Perevedentseva, H.-H. Chang, C.-H. Lin, D.-S. Sun, A. Lugovtsov, A. Priezzhev, M. Jani, and C.-L. Cheng, “The influence of nanodiamond on the oxygenation states and micro rheological properties of human Red blood cells in vitro,” J. Biomed. Optics 17(10), 101512 (2012) Crossref

17. L.-W. Tsai, Y.-C. Lin, E. Perevedentseva, A. Lugovtsov, A. Priezzhev, and C.-L. Cheng, “Nanodiamond for medical applications: interaction with blood in vitro and in vivo,” Int. J. Mol. Sci. 17(7), 1111 (2016).

18. A. Alhaddad, C. Durieu, G. Dantelle, E. L. Cam, C. Malvy, F. Treussart, and J.-R. Bertrand, “Influence of the Internalization Pathway on the Efficacy of siRNA Delivery by Cationic Fluorescent Nanodiamonds in the Ewing Sarcoma Cell Model,” PLoS ONE 7(12), e52207 (2012).

19. E. K. Chow, X.-Q. Zhang, M. Chen, R. Lam, E. Robinson, H. Huang, D. Schaffer, E. Osawa, A. Goga, and D. Ho, “Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment,” Sci. Transl. Med. 3(73), 73ra21 (2011).

20. X. Wang, X. Casuarine Low, W. Hou, L. N. Abdullah, T. B. Toh, M. M. A. Rashid, D. Ho, E. and K.-H. Chow, “Epirubicin-Adsorbed Nanodiamonds Kill Chemoresistant Hepatic Cancer Stem Cells,” ACS Nano 8 (12), 12151-12166 (2014).

21. T. Schmeller, B. Latz-Brüning, and M.Wink, “Biochemical activities of berberine, palmatine and sanguinarine mediating chemical defence against microorganisms and herbivores,” Phytochemistry 44(2), 257-266 (1997). Crossref

22. C. L. Kuo, C. W. Chi, T. and Y. Liu, “The anti-inflammatory potential of berberine in vitro and in vivo,” Cancer Lett. 203(2), 127-137 (2004). Crossref

23. S. Jie, H. Li, Y. Tian, D. Guo, J. Zhu, S. Gao, and L. Jiang, “Berberine inhibits angiogenic potential of Hep G2 cell line through VEGF down-regulation in vitro,” J. Gastroenterol. Hepatol. 26(1), 179-185 (2011).

24. M. Asai, N. Iwata, A. Yoshikawa, Y. Aizaki, S. Ishiura, T. C. Saido, and K. Maruyama., “Berberine alters the processing of Alzheimer’s amyloid precursor protein to decrease Ab secretion,” Biochem. Biophys. Res. Commun. 352(2), 498-502 (2007).

25. C. Caliceti, P. Franco, S. Spinozzi, A. Roda, and A. F. G. Cicero, “Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders,” Curr. Med. Chem. 23(14), 1460-1476 (2016).

26. J. Yin, J. Ye, and W. Jia, “Effects and mechanisms of berberine in diabetes treatment,” Acta Pharmaceutica Sinica B 2(4), 327-334 (2012). Crossref

27. S. Chen, X. Zhu, X. Lai, T. Xiao, A. Wen, and J. Zhang, “Combined cancer therapy with non-conventional drugs: all roads lead to AMPK,” Mini Rev. Med. Chem. 14(8), 642-654 (2014). Crossref

28. W. S. Kim, Y. S. Lee, S. H. Cha, H. W. Jeong, S. S. Choe, M.-R. Lee, G. T. Oh, H.-S. Park, K.-U. Lee, M. D. Lane, and J. B. Kim, “Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity,” Am. J. Physiol. Endocrinol. Metab. 296(4), E812-9 (2009).

29. S. S. Talwalkar, A. B. Vaidya, C. Godse, A. Vaidya, and R. Vaidya, “Plasmodium DNA Fluoresces With Berberine. A Novel Approach for Diagnosis of Malarial Parasites,” Am. J. Clin. Pathol. 124(3), 408-412 (2005).

30. Y.-J. Hu, Y. Liu, and X.-H. Xiao, “Investigation of the Interaction between Berberine and Human Serum Albumin,” Biomacromolecules 10(3), 517-521 (2009). Crossref

31. A. N. Colina, M. S. Díaz, and M. I. Gutiérrez, “Fluorescence of berberine in microheterogeneous systems,” J. Luminescence 144, 198-202 (2013). Crossref

32. S. Jantová, S. Letašiová, V. Brezová, L. Čipák, and J. Lábaj, “Photochemical and phototoxic activity of berberine on murine fibroblast NIH-3T3 and Ehrlich ascites carcinoma cells,” J. Photochem. Photobiol. B: Biol. 85(3), 163-176 (2006).

33. P.-H. Chung, E. Perevedentseva, J.-S. Tu, C. C. Chang, and C.-L. Cheng, “Spectroscopic study of bio-functionalized nanodiamonds,” Diam. Relat. Mater. 15(4-8), 622-625 (2006).

34. M. S. Dıaz, M. L. Freile, and M. I. Gutierrez, “Solvent effect on the UV/Vis absorption and fluorescence spectroscopic properties of berberine,” Photochem. Photobiol. Sci. 8(7), 970-974 (2009).

35. N. D. Strekal’, I. G. Motevich, J. W. Nowicky, and S. A. Maskevich, “IR absorption and surface-enhanced Raman spectra of the isoquinoline alkaloid berberine,” J. Appl. Spectr. 74(1), 31-37 (2007).

36. N. Bashmakova, S. Kutovyy, R. Zhurakivsky, D. Hovorun, and V. Yashchuk, “Vibrational spectra of berberine and their interpretation by means of DFT quantum-mechanical calculations,” Ukr. J. Phys. 56(2) 130-137 (2011).

37. M. Megyesi, L. Biczók, and I. Jablonkai, “Highly Sensitive Fluorescence Response to Inclusion Complex Formation of Berberine Alkaloid with Cucurbit[7]uril,” J. Phys. Chem. C 112(9), 3410-3416 (2008). Crossref

38. L. Xu, S. Hong, N. Sun, K. Wang, L. Zhou, L. Ji, and R. Pei, “Berberine as a novel light-up i-motif fluorescence ligand and its application in designing molecular logic systems,” Chem. Commun. 52(1), 179-182 (2016). Crossref

39. M. Cao, M. Liu, C. Cao, Y. Xia, L. Bao, Y. Jin, S. Yang, and C. Zhu, “A simple fluorescence quenching method for berberine determination using water-soluble CdTe quantum dots as probes,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 75(3), 1043-1046 (2010). Crossref

40. R. Reyes, G. Ramírez, and N. M. Delgado, “Fluorescent berberine binding as a marker of internal glycosaminoglycans sulfate in bovine oocytes and sperm cells,” Arch. Androl. 50(5), 327-332 (2004)

41. W.-Y. Wu, J.-Y. Yang, L.-M. Du, H. Wu, and C.-F. Li, “Determination of ethambutol by a sensitive fluorescent probe,” Spectrochim. Acta A Mol. Biomol. Spectrosc. 79(3), 418-422 (2011).

42. C.-Q. Zhou, J.-W. Yang, C. Dong, Y.-M. Wang, B. Sun, J.-X. Chen, Y.-S. Xu, and W.-H. Chen, “Highly selective, sensitive and fluorescent sensing of dimeric G-quadruplexes by a dimeric berberine,” Org. Biomol. Chem 14(1), 191-197 (2016). Crossref

43. M. D. Crossfield, G. Davies, A. T. Collins, and E. C. Lightowlers, “The role of defect interactions in reducing the decay time of H3 luminescence in diamond,” J. Phys. C: Solid State Phys. 7(10), 1909-1917 (1974). Crossref

44. Y.-C. Lin, K.-T. Wu, Z.-R. Lin, E. Perevedentseva, A. Karmenyan, M.-D. Lin, and C.-L. Cheng, “Nanodiamond for Biolabel and Toxicity Evaluation in the Zebrafish Embryo in vivo,” J. Biophotonics 9(8), 827–836 (2016). Crossref

45. E. Perevedentseva, N. Melnik, C.-Y. Tsai, Y.-C. Lin, M. Kazaryan, and C.-L. Cheng, “Effect of surface adsorbed proteins on the photoluminescence of nanodiamond,” J. Appl. Phys. 109(3), 034704 (2011). Crossref

46. W. Tan, Li, M. Chen, and Y. Wang, “Berberine hydrochloride: anticancer activity and nanoparticulate delivery system,” Int. J. Nanomedicine 6, 1773-1777 (2011). Crossref

47. Y.-H. Lin, J.-H. Lin, S.-C. Chou, S.-J. Chang, C.-C. Chung, Y.-S. Chen, and C.-H. Chang, “Berberine-loaded targeted nanoparticles as specific Helicobacter pylori eradication therapy: in vitro and in vivo study,” Nanomedicine (Lond) 10(1), 57-71 (2015). Crossref

48. P. R. Vuddanda, A. Mishra, S. K. Singh, and S. Singh, “Development of polymeric nanoparticles with highly entrapped herbal hydrophilic drug using nanoprecipitation technique: an approach of quality by design,” Pharm. Dev. Technol. 20(5), 579-587 (2015).

49. L. Wang, H. Li, S. Wang, R. Liu, Z. Wu, C. Wang, Y. Wang, and M. Chen, “Enhancing the Antitumor Activity of Berberine Hydrochloride by Solid Lipid Nanoparticle Encapsulation,” AAPS PharmSciTech. 15(4), 834-844 (2014). Crossref

50. V. Vaijayanthimala, D. K. Lee, S. V. Kim, A. Yen, N. Tsai, D. Ho, H.-C. Chang, and O. Shenderova., “Nanodiamond-mediated drug delivery and imaging: challenges and opportunities,” Expert. Opin. Drug. Deliv. 12(5), 735-749 (2014).

51. S Sreeja, and C. K. Nair, “Anticancer Property of Iron Oxide Nanoparticle-Drug Complexes: An In Vitro Study,” J. Environ. Pathol. Toxicol. Oncol. 34(3), 183-189 (2015).

52. M. Halimani, S. P. Chandran, S. Kashyap, V. M. Jadhav, B. L. V. Prasad, S. Hotha, and S. Maiti, “Dendritic effect of ligand-coated nanoparticles: enhanced apoptotic activity of silica-berberine nanoconjugates,” Langmuir 25(4), 2339-2347 (2009). Crossref

53. M. Thakur, A. Mewada, S. Pandey, M. Bhori, K. Singh, M. Sharon, and M. Sharon, “Milk-derived multi-fluorescent graphene quantum dot-based cancer theranostic system,” Materials Science and Engineering C 67, 468-477 (2016). Crossref

54. D. Yu, P. Ruan, Z. Meng, and J. Zhou, “The Structure-Dependent Electric Release and Enhanced Oxidation of Drug in Graphene Oxide-Based Nanocarrier Loaded with Anticancer Herbal Drug Berberine,” J. Pharm. Sci. 104, 2489-2500 (2015).

55. B. R. Wood and D. McNaughton, “Micro-Raman characterization of high- and low-spin heme moieties within single living erythrocytes,” Biopolymers 67(4-5), 259–262 (2002).

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