Dendrosomal nano-curcumin; The novel formulation to improve the anticancer properties of curcumin

Document Type : Original Research Papers

Authors

1 Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Department of Biotechnology, Faculty of advanced Medical Technology, Golestan University of Medical sciences, Gorgan, Iran

3 Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran

4 Department of Resin and Additives, Institute for Color Science and Technology

5 Department of Genetics, Faculty of biological sciences, Tarbiat Modares Univesity of Tehran, Tehran, Iran

Abstract

Curcumin is a hydrophobic polyphenol extracted from the plant curcuma longa with established
anticancer properties. However, curcumin benefits have been impaired by its very low water
solubility, low absorption, rapid metabolism and clearance from the body. Recently,
nanotechnology promises to be helpful in development of drugs delivery systems by recent
advances in macromolecular design of nanocarriers. In this review, we present the novel
generation of nano-vehicles termed dendrosomes which are readily synthesized from
esterification of oleic acid and polyethylene glycol residues. Dendrosomes efficiently
encapsulate curcumin in a spherical micellar or polymersome structures which leads to increase
aqueous solubility of this hydrophobic agent and higher bioavailability of curcumin. Anticancer
potency of this nanoformulation was confirmed in different mouse and human cancer
cells including fibrosarcoma, colon, glioblastoma, bladder, gastric, breast and hepatocellular
carcinoma in vitro and vivo. It has also demonstrated that this nano preparation has no
cytotoxicity effects on normal cells. Finally, these results introduce dendrosomal curcumin as
potent anti-tumor agent although further clinical examinations are needed.

Keywords

Main Subjects


1. Ma, Z., Haddadi, A., Molavi, O., Lavasanifar, A., Lai, R. and Samuel, J. (2008) Micelles of
poly(ethylene oxide)-b-poly(epsilon-caprolactone) as vehicles for the solubilization, stabilization,
and controlled delivery of curcumin. J Biomed Mater Res A, 86, 300-310.
2. Xiong, X.B., Binkhathlan, Z., Molavi, O. and Lavasanifar, A. (2012) Amphiphilic block copolymers:
preparation and application in nanodrug and gene delivery. Acta Biomater, 8, 2017-
2033.
3. Adams, M.L., Lavasanifar, A. and Kwon, G.S. (2003) Amphiphilic block copolymers for drug
delivery. J Pharm Sci, 92, 1343-1355.
4. Tong, R. and Cheng, J. (2007) Anticancer Polymeric Nanomedicines. Polymer Reviews, 47, 345-
381.
5. Kim, H., Kang, Y.J., Kang, S. and Kim, K.T. (2012) Monosaccharide-responsive release of
insulin from polymersomes of polyboroxole block copolymers at neutral pH. J Am Chem Soc,
134, 4030-4033.
6. Lee, J.S., Groothuis, T., Cusan, C., Mink, D. and Feijen, J. (2011) Lysosomally cleavable peptidecontaining
polymersomes modified with anti-EGFR antibody for systemic cancer chemotherapy.
Biomaterials, 32, 9144-9153.
7. Mura, S., Nicolas, J. and Couvreur, P. (2013) Stimuli-responsive nanocarriers for drug delivery.
Nat Mater, 12, 991-1003.
8. Hamidi, M., Shahbazi, M.A. and Rostamizadeh, K. (2012) Copolymers: efficient carriers for
intelligent nanoparticulate drug targeting and gene therapy. Macromol Biosci, 12, 144-164.
9. Antonietti, M. and Förster, S. (2003) Vesicles and Liposomes: A Self-Assembly Principle Beyond
Lipids. Advanced Materials, 15, 1323-1333.
10. Chen, W., Meng, F., Cheng, R. and Zhong, Z. (2010) pH-Sensitive degradable polymersomes for
triggered release of anticancer drugs: a comparative study with micelles. J Control Release, 142,
40-46.
11. Discher, D.E. and Ahmed, F. (2006) Polymersomes. Annu Rev Biomed Eng, 8, 323-341.
12. Sarbolouki, M.N., Sadeghizadeh, M., Yaghoobi, M.M., Karami, A. and Lohrasbi, T. (2000)
Dendrosomes: a novel family of vehicles for transfection and therapy. Journal of Chemical
Technology and Biotechnology, 75, 919-922.
13. Sadeghizadeh, M., Ranjbar, B., Damaghi, M., Khaki, L., Sarbolouki, M.N., Najafi, F., Parsaee, S.,
Ziaee, A.A., Massumi, M. and Lubitz, W. (2008) Dendrosomes as novel gene portersā€III. Journal
of chemical technology and biotechnology, 83, 912-920.
14. Tahmasebi Mirgani, M., Isacchi, B., Sadeghizadeh, M., Marra, F., Bilia, A.R., Mowla, S.J.,
Najafi, F. and Babaei, E. (2014) Dendrosomal curcumin nanoformulation downregulates
pluripotency genes via miR-145 activation in U87MG glioblastoma cells. International journal of
nanomedicine, 9, 403-417.
15. Erfani-Moghadam V, Nomani A, Zamani M, Yazdani Y, Najafi F and M, S. (2014) A novel diblock copolymer of (monomethoxy poly [ethylene glycol]-oleate) with a small hydrophobic fraction to make stable micelles/polymersomes for curcumin delivery to cancer cells. Int J Nanomed, 2014:9(1) 5541—5554.
16. Pourasgari, F., Ahmadian, S., Salmanian, A.H., Sarbolouki, M.N. and Massumi, M. (2009) Low
cytotoxicity effect of dendrosome as an efficient carrier for rotavirus VP2 gene transferring into a
human lung cell line. Molecular biology reports, 36, 105-109.
17. Karimi, M. (2013), In 1st Tabriz International Life Science Conference and 12th Iran Biophysical
Chemistry Conference. Tabtiz university of medical sciences, in press.
18. Anand, P., Sundaram, C., Jhurani, S., Kunnumakkara, A.B. and Aggarwal, B.B. (2008) Curcumin
and cancer: an “old-age” disease with an “age-old” solution. Cancer letters, 267, 133-164.
19. Goel, A., Kunnumakkara, A.B. and Aggarwal, B.B. (2008) Curcumin as “< i> Curecumin”:
From kitchen to clinic. Biochemical pharmacology, 75, 787-809.
20. Ravindran, J., Prasad, S. and Aggarwal, B.B. (2009) Curcumin and cancer cells: how many ways
can curry kill tumor cells selectively? The AAPS journal, 11, 495-510.
21. Anand, P., Kunnumakkara, A.B., Newman, R.A. and Aggarwal, B.B. (2007) Bioavailability of
curcumin: problems and promises. Molecular pharmaceutics, 4, 807-818.
22. Yallapu, M.M., Jaggi, M. and Chauhan, S.C. (2013) Curcumin nanomedicine: a road to cancer
therapeutics. Current pharmaceutical design, 19, 1994.
23. Babaei, E., Sadeghizadeh, M., Hassan, Z.M., Feizi, M.A.H., Najafi, F. and Hashemi, S.M. (2012)
Dendrosomal curcumin significantly suppresses cancer cell proliferation in vitro and in vivo.
International immunopharmacology, 12, 226-234.
24. Tahmasebi Mirgani, M., Sadeghizadeh, M., Najafi, F. and Mowla, S.J. (2013) Dendrosomal
curcumin induced apoptosis by suppression of pluripotency genes in 5637 bladder cancer cells.
Modares Journal of Medical Sciences: Pathobiology, 16, 23-39.
25. Esmatabadi, M.J.D., Farhangi, B., Safari, Z., Kazerooni, H., Shirzad, H., Zolghadr, F. and
Sadeghizadeh, M. (2015) Dendrosomal Curcumin Inhibits Metastatic Potential of Human SW480
Colon Cancer Cells through Down-regulation of Claudin1, Zeb1 and Hef1-1 Gene Expression.
Asian Pacific Journal of Cancer Prevention, 16, 2473-2481.
26. Erfani-Moghadam V, Nomani A, Yazdani Y, Najafi F and Sadeghizadeh M (2014) Design and
Synthesis of a Novel Dendrosome and a PEGylated PAMAM Dendrimer Nanocarrier to Improve
the Anticancer effect of Turmeric (Curcuma longa) Curcumin. Journal of Medical
Science:Pathobioligy, 17, 63-77
27. Pearson, R.T., Avila-Olias, M., Joseph, A.S., Nyberg, S. and Battaglia, G. (2013) Smart
Polymersomes: Formation, Characterisation and Applications, chapter 7 at "Smart Materials for
Drug Delivery". Royal Society of Chemistry, Cambridge, United Kingdom.
28. Erfani-Moghadam, V., (2014) Design and application of some dendritic nanocarriers on
anticancer properties of curcumin from Turmeric (Curcuma longa). PhD thesis, Tarbiat Modares
University, Tehran, Iran.
29. Alizadeh, A.M., Sadeghizadeh, M., Najafi, F., Ardestani, S.K., Erfani-Moghadam, V., Khaniki,
M., Rezaei, A., Zamani, M., Khodayari, S. and Khodayari, H. (2014) Encapsulation of Curcumin 
in Diblock Copolymer Micelles for Cancer Therapy. BioMed Research International, in press.
30. Alireza Panahi, R.N.S.a.M.S. (2012) Evaluation of Apoptosis Induction on Gastric Cancer AGS
Cells Made by Polymer Nano Curcumin. 2, 1, 200-207.
31. Birgani, M.T. (2012). Study of the Effects of Dendrosomal-Curcumin on Cell Cycle and
Pluripotency of Tumor Cell Lines and Adult Stem Cells by Measuring the Expression Profile of
OCT4, SOX-2, Nanog, miR-302 and miR-145. PhD thesis, Tarbiat Modares University, Tehran,
Iran.
32. Jordan, C.T. (2004) Cancer stem cell biology: from leukemia to solid tumors. Current opinion in
cell biology, 16, 708-712.
33. Zamani, M., Sadeghizadeh, M. and Behmanesh, M. (2014) Dendrosomal Curcumin Upregulates
Expression of the Long Non-coding RNA gene MEG3 in U87MG Glioblastoma Cells. Modares
Journal of Medical Sciences: Pathobiology, 17, 39-54.
34. amani, M., Sadeghizadeh, M., Behmanesh, M. and Najafi, F. (2015) Dendrosomal curcumin
increases expression of the long non-coding RNA gene MEG3 via up-regulation of epi-miRs in
hepatocellular cancer. Phytomedicine, 22, 961-967.
35. Shariati, M. (2013). Investigation of polymeric nanocurcumin inhibitory effect on the Human
Telomerase Reverse Transcriptase gene (hTERT) promoter through induction of TGFβ1 signaling
pathway in hepatocarcinoma cell line (Huh7). MSc thesis. Tarbiat Modares University, Tehran,
Iran.
36. Komata, T., Kanzawa, T., Kondo, Y. and Kondo, S. (2002) Telomerase as a therapeutic target for
malignant gliomas. Oncogene, 21, 656-663.
37. Najmeh Ranji, A.P.a.M.S. (2010) Study the effects of Dendrosomal curcumin in induction
apoptosis on cancer and stem cells. Modares Journal of Medical Sciences: Pathobiology, 4, 37-49.
38. Najmeh Ranji, A.P.a.M.S. (2014) Investigation of Survivin and hTERT gene expression in human
gastric adenocarcinoma cell line (AGS) treated by nano Curcumin. Journal of cellular and
Molecular researches 27, 233-241.
39. Farhangi, B., Alizadeh, A.M., Khodayari, H., Khodayari, S., Dehghan, M.J., Khori, V.,
Heidarzadeh, A., Khaniki, M., Sadeghiezadeh, M. and Najafi, F. (2015) Protective effects of
dendrosomal curcumin on an animal metastatic breast tumor. European journal of pharmacology,
758, 188-196.
40. Nazem, S. (2012). Study the effects of nano-Curcumin as a stress inhibitor on Human
Mesenchymal Stem cells exposed to hydroquinone, MSc thesis. Tarbiat Modares University,
Tehran, Iran.
41. Motahari, P., Sadeghizadeh, M., Behmanesh, M., Sabri, S. and Zolghadr, F. (2015) Generation of
stable ARE-driven reporter system for monitoring oxidative stress. DARU Journal of
Pharmaceutical Sciences, 23, 1-7.
42. Babaei, E. (2011), study of the anti-cancerous effect of dendrosomal nano-curcumin in vitro and
in vivo. Tarbiat Modares University, Tehran, Iran.