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Licensed Unlicensed Requires Authentication Published by De Gruyter October 10, 2017

A novel design of HA-coated nanoparticles co-encapsulating plasmid METase and 5-Fu shows enhanced application in targeting gastric cancer stem cells

  • Weifeng Yang , Houting Zhang and Lin Xin EMAIL logo
From the journal Biological Chemistry

Abstract

Nanoparticles (NPs) are recognized as an attractive vehicles for cancer treatment due to their targeted drug release. Gastric cancer is an important killer disease, and its therapy methods still need improvement. The NPs were prepared using a precipitation method, and were evaluated using transmission electron microscopy (TEM). MTT and Transwell assays were used to determine cell viability and apoptosis. In vivo experiments were performed to validate the effects of NPs on tumor growth. Methioninase (METase)/5-Fu co-encaspulated NPs showed highest ζ size and lowest ζ potential than other NPs. The migration and tumorsphere formation ability of CD44(+) was stronger than CD44(−). The effects of METase/5-Fu co-encaspulated NPs on inhibition cell growth was stronger than that of 5-Fu encaspulated NPs, while HA coated NPs showed significant target ability than that NPs without HA. METase supplementation promoted the inhibition effect of 5-Fu on thymidylate synthetase (TS), as well as cell apoptosis. The in vivo experiments demonstrated that HA coated NPs significantly inhibited tumor growth. It was concluded that HA-coated NPs enhance the target ability, while METase/5-Fu co-encaspulated NPs promote the inhibition effects on tumor growth in gastric cancer.

Acknowledgments

This study was supported by The National Natural Science Foundation of China (no. 81360330).

References

Alison, M.R., Lim, S.M., and Nicholson, L.J. (2011). Cancer stem cells: problems for therapy? J. Pathol. 223, 147–161.10.1002/path.2793Search in Google Scholar PubMed

Alison, M.R., Lin, W.R., Lim, S.M., and Nicholson, L.J. (2012). Cancer stem cells: in the line of fire. Cancer Treat. Rev. 38, 589–598.10.1016/j.ctrv.2012.03.003Search in Google Scholar PubMed

Bao, B., Li, Y., Ahmad, A., Azmi, A.S., Bao, G., Ali, S., Banerjee, S., Kong, D., and Sarkar, F.H. (2012). Targeting CSC-related miRNAs for cancer therapy by natural agents. Curr. Drug Targets 13, 1858.10.2174/138945012804545515Search in Google Scholar PubMed PubMed Central

Chanmee, T., Ontong, P., Kimata, K., and Itano, N. (2015). Key roles of hyaluronan and its CD44 receptor in the stemness and survival of cancer stem cells. Front. Oncol. 5, 180.10.3389/fonc.2015.00180Search in Google Scholar PubMed PubMed Central

Chen, J., Lu, H., Yan, D., Cui, F., Wang, X., Yu, F., Xue, Y., Feng, X., Wang, J., and Wang, X. (2015). PAK6 increase chemoresistance and is a prognostic marker for stage II and III colon cancer patients undergoing 5-FU based chemotherapy. Oncotarget 6, 355–367.10.18632/oncotarget.2803Search in Google Scholar PubMed PubMed Central

Cocco, E., Bellone, S., Roque, D., Guzzo, F., Gasparrini, S., Pecorelli, S., Silasi, D.A., Azodi, M., Ratner, E., and Ruterford, T. (2012). Abstract 364: In vivo targeting of CD44+ ovarian cancer stem cells (CSC) by Clostridium perfringens enterotoxin binding domain (CPE-peptide) conjugated to poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP). Cancer Res. 72, 364.10.1158/1538-7445.AM2012-364Search in Google Scholar

Dai, W., Gao, Q., Qiu, J., Yuan, J., Wu, G., and Shen, G. (2016). Quercetin induces apoptosis and enhances 5-FU therapeutic efficacy in hepatocellular carcinoma. Tumor Biol. 37, 6307–6313.10.1007/s13277-015-4501-0Search in Google Scholar PubMed

Danhier, F., Ansorena, E., Silva, J.M., Coco, R., Le, B.A., and Préat, V. (2012). PLGA-based nanoparticles: an overview of biomedical applications. J. Control Release 161, 505–522.10.1016/j.jconrel.2012.01.043Search in Google Scholar PubMed

Doolaanea, A.A., Mansor, N., Mohd Nor, N.H., and Mohamed, F. (2016). Co-encapsulation of Nigella sativa oil and plasmid DNA for enhanced gene therapy of Alzheimer’s disease. J. Microencapsul. 33, 114–126.10.3109/02652048.2015.1134689Search in Google Scholar PubMed

Gigek, C.O., Chen, E.S., Calcagno, D.Q., Wisnieski, F., Burbano, R.R., and Smith, M.A. (2016). Epigenetic mechanisms in gastric cancer. Epigenomics 4, 279–294.10.2217/epi.12.22Search in Google Scholar PubMed

Gu, M.Q., Yuan, X.B., Kang, C.S., Zhao, Y.H., Tian, N.J., Pu, P.Y., and Sheng, J. (2007). Surface biofunctionalization of PLA nanoparticles through amphiphilic polysaccharide coating and ligand coupling: evaluation of biofunctionalization and drug releasing behavior. Carbohydr. Polymers 67, 417–426.10.1016/j.carbpol.2006.06.019Search in Google Scholar

Guo, H., Lishko, V.K., Herrera, H., Groce, A., Kubota, T., and Hoffman, R.M. (1993a). Therapeutic tumor-specific cell cycle block induced by methionine starvation in vivo. Cancer Res. 53, 5676–5679.Search in Google Scholar

Guo, H.Y., Herrera, H., Groce, A., and Hoffman, R.M. (1993b). Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture. Cancer Res. 53, 2479–2483.Search in Google Scholar

Hoffman, R.M. (1984). Altered methionine metabolism, DNA methylation and oncogene expression in carcinogenesis. A review and synthesis. Biochim. Biophys. Acta 738, 49–87.Search in Google Scholar

Hoffman, R.M. (2015). Development of recombinant methioninase to target the general cancer-specific metabolic defect of methionine dependence: a 40-year odyssey. Expert Opin. Biol. Ther. 15, 21–31.10.1517/14712598.2015.963050Search in Google Scholar

Karimi, M., Eslami, M., Sahandi-Zangabad, P., Mirab, F., Farajisafiloo, N., Shafaei, Z., Ghosh, D., Bozorgomid, M., Dashkhaneh, F., and Hamblin, M.R. (2016). pH-Sensitive stimulus-responsive nanocarriers for targeted delivery of therapeutic agents. Wiley Interdisciplinary Rev. Nanomed. Nanobiotechnol. 8, 696.10.1002/wnan.1389Search in Google Scholar

Larzabal, L., El-Nikhely, N., Redrado, M., Seeger, W., Savai, R., and Calvo, A. (2013). Differential effects of drugs targeting cancer stem cell (CSC) and non-CSC populations on lung primary tumors and metastasis. PLoS One 8, e79798.10.1371/journal.pone.0079798Search in Google Scholar

Li, Y.P., Pei, Y.Y., Zhang, X.Y., Gu, Z.H., Zhou, Z.H., Yuan, W.F., Zhou, J.J., Zhu, J.H., and Gao, X.J. (2001). PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats. J. Control. Release 71, 203–211.10.1016/S0168-3659(01)00218-8Search in Google Scholar

Machover, D., Zittoun, J., Saffroy, R., Broët, P., Giraudier, S., Magnaldo, T., Goldschmidt, E., Debuire, B., Orrico, M., and Tan, Y. (2002). Treatment of cancer cells with methioninase produces DNA hypomethylation and increases DNA synthesis. Cancer Res. 62, 4685.Search in Google Scholar

Mărgăritescu, C., Pirici, D., Simionescu, C., and Stepan, A. (2011). The utility of CD44, CD117 and CD133 in identification of cancer stem cells (CSC) in oral squamous cell carcinomas (OSCC). Rom J Morphol Embryol 52, 985.Search in Google Scholar

Mecham, J.O., Rowitch, D., Wallace, C.D., Stern, P.H., and Hoffman, R.M. (1983). The metabolic defect of methionine dependence occurs frequently in human tumor cell lines. Biochem. Biophys. Res. Commun. 117, 429–434.10.1016/0006-291X(83)91218-4Search in Google Scholar

Metcalfe, C. and de Sauvage, F.J. (2013). A tumor-specific stem cell. Nat. Genet. 45, 7.10.1038/ng.2502Search in Google Scholar PubMed

Perez, A., Pereira, L., Neskey, D., Goodwin, W., Slingerland, J., and Franzmann, E. (2009). Abstract #4902: CD44, CD29 and CD133 as potential markers for cancer stem cells (CSC) in head and neck squamous cell carcinoma (HNSCC). Am. J. Physiol. Renal Physiol. 296, F1477–F1483.Search in Google Scholar

Qiao, S., Zhao, Y., Shuai, G., Yong, L., Hou, X., Yi, L., Lin, F.H., Yao, L., and Tian, W. (2016). A novel double-targeted nondrug delivery system for targeting cancer stem cells. Int. J. Nanomed. 11, 6667.10.2147/IJN.S116230Search in Google Scholar PubMed PubMed Central

Shen, S., Xia, J.X., and Wang, J. (2016). Nanomedicine-mediated cancer stem cell therapy. Biomaterials 74, 1–18.10.1016/j.biomaterials.2015.09.037Search in Google Scholar PubMed

Song, Q. (2016). Study on the effect of radiotherapy in the treatment of gastric cancer. China Foreign Medic Treatment 3, 8–10.Search in Google Scholar

Tan, Y., Xu, M., Tan, X., Tan, X., Wang, X., Saikawa, Y., Nagahama, T., Sun, X., Lenz, M., and Hoffman, R.M. (1997). Overexpression and large-scale production of recombinant L-methionine-α-deamino-gamma-mercaptomethane-lyase for novel anticancer therapy. Protein Expr. Purif. 9, 233–245.10.1006/prep.1996.0700Search in Google Scholar PubMed

Tan, Y., Sun, X., Xu, M., Tan, X., Sasson, A., Rashidi, B., Han, Q., Tan, X., Wang, X., An, Z., et al. (1999). Efficacy of recombinant methioninase in combination with cisplatin on human colon tumors in nude mice. Clin. Cancer Res. 5, 2157–2163.Search in Google Scholar

Tan, Y., Xu, M., and Hoffman, R.M. (2010a). Broad selective efficacy of recombinant methioninase and polyethylene glycol-modified recombinant methioninase on cancer cells in vitro. Anticancer Res. 30, 1041–1046.Search in Google Scholar

Tan, Y., Xu, M., and Hoffman, R.M. (2010b). Broad selective efficacy of rMETase and PEG-rMETase on cancer cells in vitro. Anticancer Res. 30, 793–798.Search in Google Scholar

Wang, S.L. (2012). Significances of CD44 as surface marker of gastric cancer cells. Chinese J. Cancer Prevent. Treat. 19, 1911–1914.Search in Google Scholar

Wang, C.H., Chiou, S.H., Chou, C.P., Chen, Y.C., Huang, Y.J., and Peng, C.A. (2011). Photothermolysis of glioblastoma stem-like cells targeted by carbon nanotubes conjugated with CD133 monoclonal antibody. Nanomed. Nanotechnol. Biol. Med. 7, 69.10.1016/j.nano.2010.06.010Search in Google Scholar PubMed

Wang, D., Huang, J., Wang, X., Yu, Y., Zhang, H., Chen, Y., Liu, J., Sun, Z., Zou, H., and Sun, D. (2013). The eradication of breast cancer cells and stem cells by 8-hydroxyquinoline-loaded hyaluronan modified mesoporous silica nanoparticle-supported lipid bilayers containing docetaxel. Biomaterials 34, 7662.10.1016/j.biomaterials.2013.06.042Search in Google Scholar PubMed

Wang, H., Guo, T., Yang, Y., and Huang, X. (2016). Postoperative chemoradiotherapy versus postoperative chemotherapy for gastric cancer with concurrent completely resected D2 lymphadenectomy: a meta-analysis of the efficacy and toxic-side effects. Chin. J. Gastroenterol. Hepatol. 25, 35–42.Search in Google Scholar

Xin, L., Caot, J.Q., Liu, C., Zeng, F., Cheng, H., Hu, X.Y., and Shao, J.H. (2015). Evaluation of rMETase-loaded stealth PLGA/liposomes modified with anti-CAGE scFV for treatment of gastric carcinoma. J. Biomed. Nanotechnol. 11, 1153.10.1166/jbn.2015.2062Search in Google Scholar PubMed

Yang, H., Zhao, G., and Zheng, H. (2015a). Therapeutic effects of laparotomy and laparoscopic surgery on patients with gastric cancer. Pak. J. Med. Sci. 31, 572–575.Search in Google Scholar

Yang, J., Huang, J., Yang, Y., Fan, N., Zhang, X., Wang, S., Li, J., and Meng, J. (2015b). Confocal laser endoscopy in the diagnosis for abdominal lymph node metastasis of gastric cancer. Int. J. Clin. Exp. Med. 8, 8905.Search in Google Scholar

Yano, S., Li, S., Han, Q., Tan, Y., Bouvet, M., Fujiwara, T., and Hoffman, R.M. (2014). Selective methioninase-induced trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity. Oncotarget 5, 8729–8736.10.18632/oncotarget.2369Search in Google Scholar PubMed PubMed Central

Yao, H.J., Zhang, Y.G., Sun, L., and Liu, Y. (2014). The effect of hyaluronic acid functionalized carbon nanotubes loaded with salinomycin on gastric cancer stem cells. Biomaterials 35, 9208–9223.10.1016/j.biomaterials.2014.07.033Search in Google Scholar PubMed

Yoon, C., Park, D.J., Schmidt, B., Thomas, N.J., Lee, H.J., Kim, T.S., Janjigian, Y.Y., Cohen, D.J., and Yoon, S.S. (2014). CD44 expression denotes a subpopulation of gastric cancer cells in which Hedgehog signaling promotes chemotherapy resistance. Clin. Cancer Res. 20, 3974–3988.10.1158/1078-0432.CCR-14-0011Search in Google Scholar PubMed PubMed Central

Yoshioka, T., Wada, T., Uchida, N., Maki, H., Yoshida, H., Ide, N., Kasai, H., Hojo, K., Shono, K., Maekawa, R., et al. (1998). Anticancer efficacy in vivo and in vitro, synergy with 5-fluorouracil, and safety of recombinant methioninase. Cancer Res. 58, 2583–2587.Search in Google Scholar

Yu, J.W., Wu, J.G., Tajima, Y., Li, X.Q., Du, G.Y., Zheng, L.H., Zhang, B., Ni, X.C., and Jiang, B.J. (2011). Study on lymph node metastasis correlated to lymphangiogenesis, lymphatic vessel invasion, and lymph node micrometastasis in gastric cancer. J. Surg. Res. 168, 188.10.1016/j.jss.2009.10.030Search in Google Scholar PubMed

Received: 2017-7-25
Accepted: 2017-9-27
Published Online: 2017-10-10
Published in Print: 2018-2-23

©2018 Walter de Gruyter GmbH, Berlin/Boston

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