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Research Article

Anti-migratory and increased cytotoxic effects of novel dual drug-loaded complex hybrid micelles in triple negative breast cancer cells

Rajaletchumy Veloo Kutty1,§Chor Yong Tay1,§Chen Siew Lim1Si-Shen Feng1,2( )David Tai Leong1,3( )
Department of Chemical and Biomolecular EngineeringNational University of Singapore4 Engineering DriveSingapore117585Singapore
International Joint Cancer InstituteThe Second Military Medical University800 Xiang Yin RoadShanghai200433China
NUS Graduate School for Integrative Science and EngineeringNational University of Singapore28 Medical DriveSingapore117456Singapore

§ These authors contributed equally to this work.

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Abstract

A polymer-based nanocarrier was developed for the co-delivery of epigenetic and chemotherapeutic drugs. The sterically stabilized hybrid micelle system uses micelles composed of D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) and 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000). In this study, suberoylanilide hydroxamic acid (SAHA) and paclitaxel were used as model drugs for combination chemotherapy to enhance therapeutic efficiency in targeting mesenchyme-like triple negative breast cancer (TNBC) cells. Combination therapy of paclitaxel and SAHA in a dual drug micelle system, (P + S)mic, exhibited an IC50 value of 0.52 μg/mL, which is about 5.91-fold more cytotoxic than the mere combination of free drugs (P + S). Furthermore, the (P + S)mic formulation was far more effective at inhibiting cell migration by more than 3.4-fold than the control. Thus, our findings show that the co-delivery of these drugs using the micelle system greatly enhances their therapeutic effect at a lower dosage, thereby minimizing toxicity. In addition, this formulation is proved to be remarkably effective in preventing cell migration at low dosage.

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References

1

Baylin, S. B. Resistance, epigenetics and the cancer ecosystem. Nat. Med. 2011, 17, 288-289.

2

Setyawati, M. I.; Tay, C. Y.; Leong, D. T. Exploiting cancer's antioxidative weakness through p53 with nanotoxicology. Nanomedicine 2014, 9, 369-371.

3

Jones, P. A.; Laird, P. W. Cancer epigenetics comes of age. Nat. Genet. 1999, 21, 163-167.

4

Portela, A.; Esteller, M. Epigenetic modifications and human disease. Nat. Biotechnol. 2010, 28, 1057-1068.

5

Wolffe, A. P.; Matzke, M. A. Epigenetics: Regulation through repression. Science 1999, 286, 481-486.

6

Momparler, R. L. Cancer epigenetics. Oncogene 2003, 22, 6479-6483.

7

Yoo, C. B.; Jones, P. A. Epigenetic therapy of cancer: Past, present and future. Nat. Rev. Drug Discov. 2006, 5, 37-50.

8

Devinoy, E.; Rijnkels, M. Epigenetics in mammary gland biology and cancer. J. Mammary Gland Biol. Neoplasia 2010, 15, 1-4.

9

Baylin, S. B.; Herman, J. G.; Graff, J. R.; Vertino, P. M.; Issa, J. P. Alterations in DNA methylation: A fundamental aspect of neoplasia. Adv. Cancer Res. 1998, 72, 141-196.

10

Herman, J. G.; Baylin, S. B. Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 2003, 349, 2042-2054.

11

Grant, S.; Easley, C.; Kirkpatrick, P. V. Nat. Rev. Drug Discov. 2007, 6, 21-22.

12

Marks, P. A.; Breslow, R. Dimethyl sulfoxide to vorinostat: Development of this histone deacetylase inhibitor as an anticancer drug. Nat. Biotechnol. 2007, 25, 84-90.

13

Cortez, C. C.; Jones, P. A. Chromatin, cancer and drug therapies. Mutat. Res. -Fundam. Mol. Mech. Mutagen. 2008, 647, 44-51.

14

Dokmanovic, M.; Clarke, C.; Marks, P. A. Histone deacetylase inhibitors: Overview and perspectives. Mol. Cancer Res. 2007, 5, 981-989.

15

Carew, J. S.; Giles, F. J.; Nawrocki, S. T. Histone deacetylase inhibitors: Mechanisms of cell death and promise in combination cancer therapy. Cancer Lett. 2008, 269, 7-17.

16

McGrogan, B. T.; Gilmartin, B.; Carney, D. N.; McCann, A. Taxanes, microtubules and chemoresistant breast cancer. Biochim. Biophys. Acta 2008, 1785, 96-132.

17

Gascoigne, K. E.; Taylor, S. S. How do anti-mitotic drugs kill cancer cells? J. Cell Sci. 2009, 122, 2579-2585.

18

Kavallaris, M. Microtubules and resistance to tubulin-binding agents. Nat. Rev. Cancer 2010, 10, 194-204.

19

Angelucci, A.; Mari, M.; Millimaggi, D.; Giusti, I.; Carta, G.; Bologna, M.; Dolo, V. Suberoylanilide hydroxamic acid partly reverses resistance to paclitaxel in human ovarian cancer cell lines. Gynecol. Oncol. 2010, 119, 557-563.

20

Cooper, A. L.; Greenberg, V. L.; Lancaster, P. S.; van Nagell, J. R.; Zimmer, S. G.; Modesitt, S. C. In vitro and in vivo histone deacetylase inhibitor therapy with suberoylanilide hydroxamic acid (SAHA) and paclitaxel in ovarian cancer. Gynecol. Oncol. 2007, 104, 596-601.

21

Dietrich, C. S.; Greenberg, V. L.; DeSimone, C. P.; Modesitt, S. C.; van Nagell, J. R.; Craven, R.; Zimmer, S. G. Suberoylanilide hydroxamic acid (SAHA) potentiates paclitaxel induced apoptosis in ovarian cancer cell lines. Gynecol. Oncol. 2010, 116, 126-130.

22

Cai, Y. Y.; Yap, C. W.; Wang, Z.; Ho, P. C.; Chan, S. Y.; Ng, K. Y.; Ge, Z. G.; Lin, H. S. Solubilization of vorinostat by cyclodextrins. J. Clin. Pharm. Ther. 2010, 35, 521-526.

23

Hu, C. M. J.; Aryal, S.; Zhang, L. Nanoparticle-assisted combination therapies for effective cancer treatment. Ther. Deliv. 2010, 1, 323-334.

24

Cho, K.; Wang, X.; Nie, S.; Chen, Z.; Shin, D. M. Therapeutic nanoparticles for drug delivery in cancer. Clin. Cancer Res. 2008, 14, 1310-1316.

25
Alexis, F.; Pridgen, E. M.; Langer, R.; Farokhzad, O. C. Nanoparticle technologies for cancer therapy. In Handbook of Experimental Pharmacology (Volume 197). Rosenthal, W., Ed. Springer Science+Business Media: Heidelberg, 2010, pp 55-86.https://doi.org/10.1007/978-3-642-00477-3_2
26

Xing, R.; Bhirde, A. A.; Wang, S.; Sun, X.; Liu, G.; Hou, Y.; Chen, X. Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles. Nano Res. 2012, 6, 1-9.

27

Chen, H.; Yeh, J.; Wang, L.; Khurshid, H.; Peng, N.; Wang, A. Y.; Mao, H. Preparation and control of the formation of single core and clustered nanoparticles for biomedical applications using a versatile amphiphilic diblock copolymer. Nano Res. 2010, 3, 852-862.

28

Muthu, M. S.; Kutty, R. V.; Luo, Z.; Xie, J.; Feng, S. S. Theranostic vitamin E TPGS micelles of transferrin conjugation for targeted co-delivery of docetaxel and ultra bright gold nanoclusters. Biomaterials 2014, 39, 234-248.

29

Li, Y.; Zheng, S.; Liang, X.; Jin, Y.; Wu, Y.; Bai, H.; Liu, R.; Dai, Z.; Liang Z.; Shi, T. Doping hydroxylated cationic lipid into PEGylated cerasome boosts in vivo siRNA transfection efficacy. Bioconjug. Chem. 2014, 25, 2055-2066.

30

Tay, C. Y.; Yu, Y.; Setyawati, M. I.; Xie, J.; Leong, D. T. Presentation matters: Identity of gold nanocluster capping agent governs intracellular uptake and cell metabolism. Nano Res. 2014, 7, 805-815.

31

Tay, C. Y.; Fang, W.; Setyawati, M. I.; Chia, S. L.; Tan, K. S.; Hsu, C.; Hong, C. H.; Leong, D. T. Nano-hydroxyapatite and nano-titanium dioxide exhibit different subcellular distribution and apoptotic profile in human oral epithelium. ACS Appl. Mater. Interfaces 2014, 6, 6248-6256.

32

Setyawati, M. I.; Kutty, R. V.; Tay, C. Y.; Yuan, X.; Xie, J.; Leong, D. T. Novel theranostic DNA nanoscaffolds for the simultaneous detection and killing of Escherichia coli and Staphylococcus aureus. ACS Appl. Mater. Interfaces 2014, 6, 21822-21831.

33

Setyawati, M. I.; Tay, C. Y.; Chia, S. L.; Goh, S. L.; Fang, W.; Neo, M. J.; Chong, H. C.; Tan, S. M.; Loo, S. C. J.; Ng, K. W. et al. Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin. Nat. Commun. 2013, 4, 1673.

34

Tay, C. Y.; Setyawati, M. I.; Xie, J.; Parak, W. J.; Leong, D. T. Back to basics: Exploiting the innate physico-chemical characteristics of nanomaterials for biomedical applications. Adv. Funct. Mater. 2014, 24, 5936-5955.

35

Leong, D. T.; Ng, K. W. Probing the relevance of 3D cancer models in nanomedicine research. Adv. Drug Deliv. Rev. 2014, 79-80, 95-106.

36

Kutty, R. V.; Feng, S. S. Cetuximab conjugated vitamin E TPGS micelles for targeted delivery of docetaxel for treatment of triple negative breast cancers. Biomaterials 2013, 34, 10160-10171.

37

Kutty, R. V.; Wei Leong, D. T.; Feng, S. S. Nanomedicine for the treatment of triple-negative breast cancer. Nanomedicine 2014, 9, 561-564.

38

Sun, Z.; Wang, W.; Meng, J.; Chen, S.; Xu, H.; Yang, X. D. Multi-walled carbon nanotubes conjugated to tumor protein enhance the uptake of tumor antigens by human dendritic cells in vitro. Cell Res. 2010, 20, 1170-1173.

39

Ma, K.; Wang, D. D.; Lin, Y.; Wang, J.; Petrenko, V.; Mao, C. Synergetic targeted delivery of sleeping-beauty transposon system to mesenchymal stem cells using LPD nanoparticles modified with a phage-displayed targeting peptide. Adv. Funct. Mater. 2013, 23, 1172-1181.

40

Zhang, Z.; Tan, S.; Feng, S. S. Vitamin E TPGS as a molecular biomaterial for drug delivery. Biomaterials 2012, 33, 4889-4906.

41

Mu, L.; Feng, S. S. Vitamin E TPGS used as emulsifier in the solvent evaporation/extraction technique for fabrication of polymeric nanospheres for controlled release of paclitaxel (Taxol). J. Control. Release 2002, 80, 129-144.

42

Muthu, M. S.; Leong, D. T.; Mei, L.; Feng, S. S. Nanotheranostics—Application and further development of nanomedicine strategies for advanced theranostics. Theranostics 2014, 4, 660-677.

43

Sarfstein, R.; Bruchim, I.; Fishman, A.; Werner, H. The mechanism of action of the histone deacetylase inhibitor vorinostat involves interaction with the insulin-like growth factor signaling pathway. PLoS One 2011, 6, e24468.

44

Rodriguez, L. G.; Wu, X.; Guan, J. Wound-healing assay. Methods Mol. Biol. 2005, 294, 23-29.

45

Sawant, R. R.; Torchilin, V. P. Polymeric micelles: Polyethylene glycol-Phosphatidylethanolamine (PEG-PE)- based micelles as an example. Methods Mol. Biol. 2010, 624, 131-149.

46

Taurin, S.; Nehoff, H.; Greish, K. Anticancer nanomedicine and tumor vascular permeability: Where is the missing link? J. Control. Release 2012, 164, 265-275.

47

Verma, M. S.; Liu, S. Y.; Chen, Y. Y.; Meerasa, A.; Gu, F. X. Size-tunable nanoparticles composed of dextran-b poly(D, Llactide) for drug delivery applications. Nano Res. 2011, 5, 49-61.

48

Shan, X.; Yuan, Y.; Liu, C.; Tao, X.; Sheng, Y.; Xu, F. Influence of PEG chain on the complement activation suppression and longevity in vivo prolongation of the PCL biomedical nanoparticles. Biomed. Microdevices 2009, 11, 1187-1194.

49

Gill, K. K.; Kaddoumi, A.; Nazzal, S. Mixed micelles of PEG2000-DSPE and vitamin-E TPGS for concurrent delivery of paclitaxel and parthenolide: Enhanced chemosenstization and antitumor efficacy against non-small cell lung cancer (NSCLC) cell lines. Eur. J. Pharm. Sci. 2012, 46, 64-71.

50

Mu, L.; Elbayoumi, T. A.; Torchilin, V. P. Mixed micelles made of poly(ethylene glycol)-phosphatidylethanolamine conjugate and D-α-tocopheryl polyethylene glycol 1000 succinate as pharmaceutical nanocarriers for camptothecin. Int. J. Pharm. 2005, 306, 142-149.

51

Owen, S. C.; Chan, D. P. Y.; Shoichet, M. S. Polymeric micelle stability. Nano Today 2012, 7, 53-65.

52

Feng, S.S.; Zhao, L.; Zhang, Z.; Bhakta, G.; Win, K. Y.; Dong, Y.; Chien, S. Chemotherapeutic engineering: Vitamin E TPGS-emulsified nanoparticles of biodegradable polymers realized sustainable paclitaxel chemotherapy for 168 h in vivo. Chem. Eng. Sci. 2007, 62, 6641-6648.

53

Hasan, A. S.; Socha, M.; Lamprecht, A.; Ghazouani, F. E.; Sapin, A.; Hoffman, M.; Maincent, P.; Ubrich, N. Effect of the microencapsulation of nanoparticles on the reduction of burst release. Int. J. Pharm. 2007, 344, 53-61.

54
Chiao, J.; Paradise, C.; Frankel, S. R.; Ramalingam, S. S.; Belani, C. Methods of treating cancers with SAHA, carboplatin, and paclitaxel and other combination therapies. U.S. Patent 20090105329, April 23, 2009.
55

Zhao, B.; Wang, X. Q.; Wang, X. Y.; Zhang, H.; Dai, W. B.; Wang, J.; Zhong, Z. L.; Wu, H. N.; Zhang, Q. Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure. Part. Fibre Toxicol. 2013, 10, 47.

56

Tan, G. R.; Feng, S. S.; Leong, D. T. The reduction of anticancer drug antagonism by the spatial protection of drugs with PLA-TPGS nanoparticles. Biomaterials 2014, 35, 3044-3051.

57

Modesitt, S. C.; Parsons, S. J. In vitro and in vivo histone deacetylase inhibitor therapy with vorinostat and paclitaxel in ovarian cancer models: Does timing matter? Gynecol. Oncol. 2010, 119, 351-357.

58

Mi, Y.; Liu, X. L.; Zhao, J.; Ding, J.; Feng, S. S. Multimodality treatment of cancer with herceptin conjugated, thermomagnetic iron oxides and docetaxel loaded nanoparticles of biodegradable polymers. Biomaterials 2012, 33, 7519-7529.

59

Yvon, A. M. C.; Wadsworth, P.; Jordan, M. A. Taxol suppresses dynamics of individual microtubules in living human tumor cells. Mol. Biol. Cell 1999, 10, 947-959.

60

Terzis, A. J.; Thorsen, F.; Heese, O.; Visted, T.; Bjerkvig, R.; Dahl, O.; Arnold, H.; Gundersen, G. Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (taxol) in vitro. Br. J. Cancer 1997, 75, 1744-1752.

61

An, Z.; Gluck, C. B.; Choy, M. L.; Kaufman, L. J. Suberoylanilide hydroxamic acid limits migration and invasion of glioma cells in two and three dimensional culture. Cancer Lett. 2010, 292, 215-227.

62

Chong, W.; Li, Y.; Liu, B.; Zhao, T.; Fukudome, E. Y.; Liu, Z.; Smith, W. M.; Velmahos, G. C.; deMoya, M. A.; Alam, H. B. Histone deacetylase inhibitor suberoylanilide hydroxamic acid attenuates Toll-like receptor 4 signaling in lipopolysaccharide-stimulated mouse macrophages. J. Surg. Res. 2012, 178, 851-859.

63

Westerlund, A.; Hujanen, E.; Höyhtyä, M.; Puistola, U.; Turpeenniemi-Hujanen, T. Ovarian cancer cell invasion is inhibited by paclitaxel. Clin. Exp. Metastasis 1997, 15, 318-328.

64

Koo, C. X.; Fang, W.; Salto-Tellez, M.; Leong, D. T. Coexpressing shRNA with fluorescence tags for quantification of cell migration studies. Mol. Biol. Rep. 2012, 39, 7695- 7703.

65

Leong, D. T.; Lim, J.; Goh, X.; Pratap, J.; Pereira, B. P.; Kwok, H. S.; Nathan, S. S.; Dobson, J. R.; Lian, J. B.; Ito, Y. et al. Cancer-related ectopic expression of the bone-related transcription factor RUNX2 in non-osseous metastatic tumor cells is linked to cell proliferation and motility. Breast Cancer Res. 2010, 12, R89.

Nano Research
Pages 2533-2547
Cite this article:
Kutty RV, Tay CY, Lim CS, et al. Anti-migratory and increased cytotoxic effects of novel dual drug-loaded complex hybrid micelles in triple negative breast cancer cells. Nano Research, 2015, 8(8): 2533-2547. https://doi.org/10.1007/s12274-015-0760-8

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Received: 14 January 2015
Revised: 26 February 2015
Accepted: 02 March 2015
Published: 29 August 2015
© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2015
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