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Tricalcium Phosphate Nanostructures Loaded with Bisphosphonate as Potential Anticancer Agents
M. Rahmanian1, S.M. Naghib2, A. Seyfoori1, A.A. Zare1,3, K. Majidzadeh-A1,4, L. Farahmand1,3
1 Biomaterials and Tissue Engineering Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
2 Nanobioengineering Division, Nanotechnology Department, School of New Technologies, Iran University of Science and Technology (IUST), P.O. Box 16846 – 13114, Tehran, Iran.
3 Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institut, ACECR, Tehran, Iran
4 Genetics Department, Breast Cancer Research Center, Motamed Cancer Institut, ACECR, Tehran, Iran
received April 30, 2017, received in revised form June 25, 2017, accepted July 15, 2017
Vol. 8, No. 4, Pages 505-512 DOI: 10.4416/JCST2017-00029
Abstract
Nanostructured calcium phosphate carriers are emerging as a bisphosphonate delivery system that has demonstrated inhibitory effects in preventing bone metastasis, thereby improving the treatment of breast cancer. In this research, the inhibitory effect of loaded zoledronic acid (ZA) in tricalcium phosphate nanostructures (TCPNs) synthesized with the co-precipitation method was investigated. The results of microstructural analysis indicated that the sintering temperature has a slight influence on the synthesized crystallite size. The sintered crystallite size of tricalcium phosphate (TCP) at 800 °C (β-TCP) and 1450 °C (α-TCP) was calculated to be in the nanoscale range. The inhibitory effect of TCPNs (with different phases) on cancer cell lines including MCF-7 (breast cancer) and G-292 (osteosarcoma cancer) was investigated. In vitro results confirmed that the TCPNs were able to inhibit the proliferation of breast cancer cells. Experimental results of MCF-7 cell culture after two days proved that the growth of the cancer cells was inhibited by about 61 % and 83 % after treatment with β-TCP and α-TCP, respectively. Bisphosphonate-loaded TCPNs had no toxicity according to MTT assay results, but did have an inhibitory effect on MCF-7 cancer cells. The time dependence of ZA drug release from α and β-TCP and its effect on MCF-7 and G-292 cell treatment was investigated. The results suggested that TCPNs are promising materials that could be developed for treating local bone and breast cancers.
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Keywords
MCF-7, G-292, tricalcium phosphate, nanomedicine, inhibitory effect
References
1 Weigelt, B., Peterse, J.L., Van't Veer, L.J.: Breast cancer metastasis: Markers and models, Nat. Rev. Cancer, 5, 591 – 602, (2005).
2 Joyce, J.A., Pollard, J.W.: Microenvironmental regulation of metastasis, Nat. Rev. Cancer, 9, 239 – 252, (2009).
3 Clemons, M., Gelmon, K., Pritchard, K., Paterson, A.: Bone-targeted agents and skeletal-related events in breast cancer patients with bone metastases: The state of the art, Curr. Oncol., 19, 259 – 268, (2012).
4 Frede, A., Neuhaus, B., Klopfleisch, R., Walker, C., Buer, J., Müller, W., Epple, M., Westendorf, A.M.: Colonic gene silencing using siRNA-loaded calcium phosphate/PLGA nanoparticles ameliorates intestinal inflammation in vivo, J. Control. Release, 222, 86 – 96, (2016).
5 Gao, X., Lan, J., Jia, X., Cai, Q., Yang, X.: Improving interfacial adhesion with epoxy matrix using hybridized carbon nanofibers containing calcium phosphate nanoparticles for bone repairing, Mater. Sci. Eng. C., 61, 174 – 179, (2016).
6 Karimi, M., Hesaraki, S., Alizadeh, M., Kazemzadeh, A.: Synthesis of calcium phosphate nanoparticles in deep-eutectic choline chloride-urea medium: Investigating the role of synthesis temperature on phase characteristics and physical properties, Ceram. Int., 42, 2780 – 2788, (2016).
7 Qian, J., Ma, J., Su, J., Yan, Y., Li, H., Shin, J.-W., Wei, J., Zhao, L.: PHBV-based ternary composite by intermixing of magnesium calcium phosphate nanoparticles and zein: In vitro bioactivity, degradability and cytocompatibility, Eur. Polym. J., 75, 291 – 302, (2016).
8 Zhang, J., Sun, X., Shao, R., Liang, W., Gao, J., Chen, J.: Polycation liposomes combined with calcium phosphate nanoparticles as a non-viral carrier for siRNA delivery, J. Drug Deliv. Sci. Technol., 30, 1 – 6, (2015).
9 Mi, P., Kokuryo, D., Cabral, H., Kumagai, M., Nomoto, T., Aoki, I., Terada, Y., Kishimura, A., Nishiyama, N., Kataoka, K.: Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors, J. Control. Release, 174, 63 – 71, (2014).
10 Koshkaki, M.R., Ghassai, H., Khavandi, A., Seyfoori, A., Molazemhosseini, A.: Effects of formaldehyde solution and nanoparticles on mechanical properties and biodegradation of gelatin/nano β-TCP scaffolds, Iran. Polym. J., 22, 653 – 664, (2013).
11 Zekri, J., Mansour, M., Karim, S.M.: The anti-tumour effects of zoledronic acid, J. Bone. Oncol., 3, 25 – 35, (2014).
12 Mitri, Z., Nanda, R., Blackwell, K., Costelloe, C.M., Hood, I., Wei, C., Brewster, A.M., Ibrahim, N.K., Koenig, K.B., Hortobagyi, G.N.: TBCRC-010: Phase I/II study of dasatinib in combination with zoledronic acid for the treatment of breast cancer bone metastasis, Clin. Cancer Res., 22, 5706 – 5712, (2016).
13 Bose, S., Tarafder, S.: Calcium phosphate ceramic systems in growth factor and drug delivery for bone tissue engineering: a review, Acta. Biomater., 8, 1401 – 1421, (2012).
14 Barrère, F., van Blitterswijk, C.A., de Groot, K.: Bone regeneration: molecular and cellular interactions with calcium phosphate ceramics, Int. J. Nanomedicine, 1, 317 – 332, (2006).
15 Ottewell, P.D., Mönkkönen, H., Jones, M., Lefley, D.V., Coleman, R.E., Holen, I.: Antitumor effects of doxorubicin followed by zoledronic acid in a mouse model of breast cancer, J. Natl. Cancer Inst., 100, 1167 – 1178, (2008).
16 Brufsky, A.M., Bosserman, L.D., Caradonna, R.R., Haley, B.B., Jones, C.M., Moore, H.C., Jin, L., Warsi, G.M., Ericson, S.G., Perez, E.A.: Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST study 36-month follow-up results, Clin. Breast Cancer, 9, 77 – 85, (2009).
17 Meena, R., Kesari, K.K., Rani, M., Paulraj, R.: Effects of hydroxyapatite nanoparticles on proliferation and apoptosis of human breast cancer cells (MCF-7), J. Nanopart. Res., 14, 1 – 11, (2012).
18 Han, Y., Li, S., Cao, X., Yuan, L., Wang, Y., Yin, Y., Qiu, T., Dai, H., Wang, X.: Different inhibitory effect and mechanism of hydroxyapatite nanoparticles on normal cells and cancer cells in vitro and in vivo, Sci. Rep., 4, 7134 – 7140, (2014).
19 Liu, J., Zhao, L., Ni, L., Qiao, C., Li, D., Sun, H., Zhang, Z.: The effect of synthetic α-tricalcium phosphate on osteogenic differentiation of rat bone mesenchymal stem cells, Am. J. Transl. Res., 7, 1588 – 1601, (2015).
20 Kwon, S.-H., Jun, Y.-K., Hong, S.-H., Kim, H.-E.: Synthesis and dissolution behavior of β-TCP and HA/β-TCP composite powders, J. Eur. Ceram. Soc., 23, 1039 – 1045, (2003).
21 Erisken, C., Kalyon, D.M., Wang, H.: Functionally graded electrospun polycaprolactone and β-tricalcium phosphate nanocomposites for tissue engineering applications, Biomaterials, 29, 4065 – 4073, (2008).
22 Yuan, Y., Liu, C., Qian, J., Wang, J., Zhang, Y.: Size-mediated cytotoxicity and apoptosis of hydroxyapatite nanoparticles in human hepatoma HepG2 cells, Biomaterials, 31, 730 – 740, (2010).
23 Venkatesan, P., Puvvada, N., Dash, R., Kumar, B.P., Sarkar, D., Azab, B., Pathak, A., Kundu, S.C., Fisher, P.B., Mandal, M.: The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer, Biomaterials, 32, 3794 – 3806, (2011).
24 Li, J., Yin, Y., Yao, F., Zhang, L., Yao, K.: Effect of nano-and micro-hydroxyapatite/chitosan-gelatin network film on human gastric cancer cells, Mater. Lett., 62, 3220 – 3223, (2008).
25 Tang, W., Yuan, Y., Liu, C., Wu, Y., Lu, X., Qian, J.: Differential cytotoxicity and particle action of hydroxyapatite nanoparticles in human cancer cells, Nanomedicine, 9, 397 – 412, (2014).
26 Gu, W., Wu, C., Chen, J., Xiao, Y.: Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration, Int. J. Nanomedicine, 8, 2305 – 2317, (2013).
27 Heymann, D.: Zoledronic Acid, Encyclopedia of Cancer, Springer, Berlin Heidelberg, 2011.
28 Huang, K.-C., Cheng, C.-C., Chuang, P.-Y., Yang, T.-Y.: The effects of zoledronate on the survival and function of human osteoblast-like cells, BMC. Musculoskelet. Disord., 16, 355, (2015).
29 Gallinetti, S., Canal, C., Ginebra, M.P.: Development and characterization of biphasic hydroxyapatite/β-TCP cements, J. Am. Ceram. Soc., 97, 1065 – 1073, (2014).
30 Tadic, D., Epple, M.: A thorough physicochemical characterisation of 14 calcium phosphate-based bone substitution materials in comparison to natural bone, Biomaterials., 25, 987 – 994, (2004).
31 Choi, D., Kumta, P.N.: Mechano-chemical synthesis and characterization of nanostructured β-TCP powder, Mater. Sci. Eng. C., 27, 377 – 381, (2007).
32 Xu, Z., Liu, C., Wei, J., Sun, J.: Effects of four types of hydroxyapatite nanoparticles with different nanocrystal morphologies and sizes on apoptosis in rat osteoblasts, J. Appl. Toxicol., 32, 429 – 435, (2012).
33 Rahmanian, M., Naghib, S.M., Seyfoori, A., Zare, A.A., Sanati, H., Majidzadeh-A, K.: Inhibitory effect of tricalcium phosphate sintered at different temperatures on human breast cancer cell line MCF-7, Multidiscip. Cancer. Invest., 1, 11 – 14, (2016).
34 Rahmanian, M., Naghib, M., Seyfoori, A., Zare, A.A., Majidzadeh-A, K.: Investigation of inhibitory effect of β-tricalcium phosphate on MCF-7 Proliferation. iranian journal of breast disease, Iran. J. Breast. Dis., 9, 7 – 13, (2016).
35 Chen, T., Shukoor, M.I., Wang, R., Zhao, Z., Yuan, Q., Bamrungsap, S., Xiong, X., Tan, W.: Smart multifunctional nanostructure for targeted cancer chemotherapy and magnetic resonance imaging, ACS. Nano., 5, 7866 – 7873, (2011).
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