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Preparation, characterization, and in vitro antitumor activity of folate conjugated chitosan coated EGCG nanoparticles

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Abstract

Folate conjugated chitosan coated EGCG nanoparticles (FCS-EGCG-NPs) were prepared using the ionic gelation method with folic acid modified carboxymethyl chitosan (FA-CMC) and chitosan hydrochloride as carriers of catechin EGCG. Characteristics of FCS-EGCG-NPs were determined using transmission electron microscopy (TEM) and fourier transform infrared spectroscopy (FTIR). Synthesized FCS-EGCG-NPs were spherical in shape with a mean diameter of 400 nm. The maximum encapsulation rate of nanoparticles loaded with EGCG was 75%. FTIR spectra suggested formation of an amide linkage between carboxyl groups of FA-CMC and the amine groups of chitosan hydrochloride. FCS-EGCG-NPs demonstrated sustained release of EGCG in buffer solutions of different pH values. The antitumor activity of FCS-EGCG-NPs towards different cancer cells was also investigated. FCS-EGCG-NPs had a greater tumor inhibition effect on cancer cells having a large expression of folic acid receptors on the surface than cancer cells with lesser expression.

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References

  1. Sukhthankar M, Alberti S, Baek SJ. (-)-Epigallocatechin-3-gallate (EGCG) post-transcriptionally and post-translationally suppresses the cell proliferative protein TROP2 in human colorectal cancer cells. Anticancer Res. 30: 2497–2503 (2010)

    CAS  Google Scholar 

  2. Shankar S, Ganapathy S, Hingorani SR, Srivastava RK. EGCG inhibits growth, invasion, angiogenesis and metastasis of pancreatic cancer. Front. Biosci. 13: 440–452 (2008)

    Article  Google Scholar 

  3. Sen T, Chatterjee A. Epigallocatechin-3-gallate (EGCG) downregulates EGF-induced MMP-9 in breast cancer cells: Involvement of integrin receptor alpha 5 beta 1 in the process. Eur. J. Nutr. 50: 465–478 (2011)

    Article  CAS  Google Scholar 

  4. Landis-Piwowar K, Chen D, Chan TH, Dou QP. Inhibition of catechol-O-methyltransferase activity in human breast cancer cells enhances the biological effect of the green tea polyphenol (-)-EGCG. Oncol. Rep. 24: 563–569 (2010)

    CAS  Google Scholar 

  5. Deng YT, Lin JK. EGCG inhibits the invasion of highly invasive CL1-5 lung cancer cells through suppressing MMP-2 expression via JNK signaling and induces G2/M arrest. J. Agr. Food Chem. 59: 13318–13327 (2011)

    Article  CAS  Google Scholar 

  6. Wang H, Bian S, Yang CS. Green tea polyphenol EGCG suppresses lung cancer cell growth through upregulating miR-210 expression caused by stabilizing HIF-1 alpha. Carcinogenesis 32: 1881–1889 (2010)

    Article  Google Scholar 

  7. Choudhury SR, Balasubramanian S, Chew YC, Han B, Marquez VE, Eckert RL. (-)-Epigallocatechin-3-gallate and DZNep reduce polycomb protein level via a proteasome-dependent mechanism in skin cancer cells. Carcinogenesis 32: 1525–1532 (2011)

    Article  CAS  Google Scholar 

  8. Nandakumar V, Vaid M, Katiyar SK. (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes, Cip1/p21 and p16(INK4a), by reducing DNA methylation and increasing histones acetylation in human skin cancer cells. Carcinogenesis 32: 537–544 (2011)

    Article  CAS  Google Scholar 

  9. Siddiqui IA, Asim M, Hafeez BB, Adhami VM, Tarapore RS, Mukhtar H. Green tea polyphenol EGCG blunts androgen receptor function in prostate cancer. FASEB J. 25: 1198–1207 (2011)

    Article  CAS  Google Scholar 

  10. Tang SN, Singh C, Nall D, Meeker D, Shankar S, Srivastava RK. The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition. J. Mol. Signal. 5: 14 (2010)

    Article  Google Scholar 

  11. Singh BN, Shankar S, Srivastava RK. Green tea catechin, epigallocatechin-3-gallate (EGCG): Mechanisms, perspectives and clinical applications. Bio. Pharm. 82: 1807–1821 (2011)

    Article  CAS  Google Scholar 

  12. Mathew ME, Mohan JC, Manzoor K, Nair SV, Tamura H, Jayakumar R. Folate conjugated carboxymethyl chitosan-manganese doped zinc sulphide nanoparticles for targeted drug delivery and imaging of cancer cells. Carbohyd. Polym. 80: 442–448 (2010)

    Article  CAS  Google Scholar 

  13. Sadahiro S, Suzuki T, Maeda Y, Tanaka A, Ogoshi K, Kamijo A, Murayama C, Tsukioka S, Sakamoto E, Fukui Y, Oka T. Molecular determinants of folate levels after leucovorin administration in colorectal cancer. Cancer Chemoth. Pharm. 65: 735–742 (2010)

    Article  CAS  Google Scholar 

  14. Crane LMA, Arts HJG, van Oosten M, Low PS, van der Zee AG, van Dam GM, Bart J. The effect of chemotherapy on expression of folate receptor-alpha in ovarian cancer. Cell. Oncol. 35: 9–18 (2012)

    Article  CAS  Google Scholar 

  15. Nunez MI, Behrens C, Woods DM, Lin H, Suraokar M, Kadara H, Hofstetter W, Kalhor N, Lee JJ, Franklin W, Stewart DJ, Wistuba II. High expression of folate receptor alpha in lung cancer correlates with adenocarcinoma histology and EGFR mutation. Mod. Path. 24: 420–421 (2011)

    Google Scholar 

  16. Zhao LM, Shi LE, Zhang ZL, Chen JM, Shi DD, Yang J, Tang ZX. Preparation and application of chitosan nanoparticles and nanofibers. Brazilian J. Chem. Eng. 28: 353–362 (2011)

    CAS  Google Scholar 

  17. Bosselmann S, Williams RO. Has nanotechnology led to improved therapeutic outcomes? Drug Dev. Ind. Pharm. 38: 158–170 (2012)

    Article  CAS  Google Scholar 

  18. Gong YK, Winnik FM. Strategies in biomimetic surface engineering of nanoparticles for biomedical applications. Nanoscale 4: 360–368 (2012)

    Article  CAS  Google Scholar 

  19. Paulo CSO, Pires das Neves R, Ferreira LS. Nanoparticles for intracellular-targeted drug delivery. Nanotechnology 22: 494002 (2011)

    Article  Google Scholar 

  20. Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 3: 16–20 (2009)

    Article  CAS  Google Scholar 

  21. Hu B, Ting Y, Yang X, Tang W, Zeng X, Huang Q. Nanochemoprevention by encapsulation of (-)-epigallocatechin-3-gallate with bioactive peptides/chitosan nanoparticles for enhancement of its bioavailability. Chem. Commun. 48: 2421–2423 (2012)

    Article  CAS  Google Scholar 

  22. El-Shabouri MH. Positively charged nanoparticles for improving the oral bioavailability of cyclosporin-A. Int. J. Pharm. 249: 101–108 (2002)

    Article  CAS  Google Scholar 

  23. Hu B, Pan C, Sun Y, Hou Z, Ye H, Zeng X. Optimization of fabrication parameters to produce chitosan-tripolyphosphate nanoparticles for delivery of tea catechins. J. Agr. Food Chem. 56: 7451–7458 (2008)

    Article  CAS  Google Scholar 

  24. Sayin B, Somavarapu S, Li XW, Thanou M, Sesardic D, Alpar HO, Senel S. Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery. Int. J. Pharm. 363: 139–148 (2008)

    Article  CAS  Google Scholar 

  25. Liang J, Li F, Fang Y, Yang WJ, An XX, Zhao LY, Xin ZH, Hu QH. Response surface methodology in the optimization of tea polyphenols-loaded chitosan nanoclusters formulations. Eur. Food Res. Tech. 231: 917–924 (2010)

    Article  CAS  Google Scholar 

  26. Liang J, Li F, Fang Y, Yang WJ, An XX, Zhao LY, Xin ZH, Cao L, Hu QH. Synthesis, characterization and cytotoxicity studies of chitosan-coated tea polyphenols nanoparticles. Colloid. Surface. B 82: 297–301 (2011)

    Article  CAS  Google Scholar 

  27. Dehshahri S, Wink M, Afsharypuor S, Asghari G, Mohagheghzadeh A. Antioxidant activity of methanolic leaf extract of Moringa peregrina (Forssk.) Fiori. Res. Pharm. Sci. 2: 111–118 (2012)

    Google Scholar 

  28. Li P, Wang Y, Zeng F, Chen L, Peng Z, Kong LX. Synthesis and characterization of folate conjugated chitosan and cellular uptake of its nanoparticles in HT-29 cells. Carbohyd. Res. 346: 801–806 (2011)

    Article  CAS  Google Scholar 

  29. Kosaraju SL, D’Ath L, Lawrence A. Preparation and characterisation of chitosan microspheres for antioxidant delivery. Carbohyd. Polym. 64: 163–167 (2006)

    Article  CAS  Google Scholar 

  30. Dube A, Nicolazzo JA, Larson I. Chitosan nanoparticles enhance the intestinal absorption of the green tea catechins (+)-catechin and (-)-epigallocatechin gallate. Eur. J. Pharm. Sci. 41: 219–225 (2010)

    Article  CAS  Google Scholar 

  31. Dube A, Nicolazzo JA, Larson I. Chitosan nanoparticles enhance the plasma exposure of (-)-epigallocatechin gallate in mice through an enhancement in intestinal stability. Eur. J. Pharm. Sci. 44: 422–426 (2011)

    Article  CAS  Google Scholar 

  32. Galbiati A, Tabolacci C, Morozzo Della Rocca B, Mattioli P, Beninati S, Paradossi G, Desideri A. Targeting tumor cells through chitosan-folate modified microcapsules loaded with camptothecin. Bioconjug. Chem. 22: 1066–1072 (2011)

    Article  CAS  Google Scholar 

  33. Gong JL, Wang SM, Hu XG, Cao MM, Zhang JR. Synthesis and characterization of folic acid-conjugated chitosan nanoparticles as a tumor-targeted drug carrier. Nan Fang Yi Ke Da Xue Xue Bao (China) 28: 2183–2186 (2008)

    CAS  Google Scholar 

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Correspondence to Xiao-Chun Wan.

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Liang, J., Cao, L., Zhang, L. et al. Preparation, characterization, and in vitro antitumor activity of folate conjugated chitosan coated EGCG nanoparticles. Food Sci Biotechnol 23, 569–575 (2014). https://doi.org/10.1007/s10068-014-0078-4

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  • DOI: https://doi.org/10.1007/s10068-014-0078-4

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