Advertisement

Applied Nanoscience

, Volume 9, Issue 1, pp 7–17 | Cite as

Folate-tagged chitosan-functionalized gold nanoparticles for enhanced delivery of 5-fluorouracil to cancer cells

  • Jude Akinyelu
  • Moganavelli SinghEmail author
Original Article
  • 17 Downloads

Abstract

Nanoparticles composed of therapeutic drugs are suggested as a promising approach for improved drug delivery to tumour cells. Herein, we report the synthesis of 5-fluorouracil (5-FU) encapsulated chitosan (C) functionalized gold (G) nanoparticles (CG5-FU-NPs) and a folate (F) linked counterpart (FCG5-FU-NPs) for enhanced anticancer effects with reduced adverse reactions. Ionic complexation was used to accomplish 5-FU–excipient interaction and the drug encapsulation efficiencies of the nanoparticles were determined appropriately. UV–visible spectroscopy, TEM, FTIR and nanoparticle tracking analysis (NTA) were used to determine the physiochemical properties of the NPs. Also, dynamic dialysis method was used to determine the rate of drug release at simulated tumour and physiological pH conditions. Cell viability was investigated by the MTT assay in human breast adenocarcinoma (MCF-7), hepatocellular carcinoma (HepG2) and kidney (HEK293) cells. CG5-FU-NPs and FCG5-FU-NPs presented as spherical nanoparticles with a size range of 31–33 nm, and showed surface plasmon resonance bands (SPR) between 520 and 525 nm, thus confirming the synthesis of G-NPs. FTIR spectroscopy confirmed the presence of chitosan and folate chitosan on the nanoparticles. CG5-FU-NPs and FCG5-FU-NPs were highly stable as suggested by zeta measurements of approximately + 61.9 mV and + 57.9 mV, respectively. The NPs attained a drug encapsulation efficiency of > 70%, and produced a pH dependent release of 5-FU. Furthermore, both NPs exhibited an enhanced tumour-specific cytotoxicity compared to the free drug, with FCG5-FU-NPs showing significant targeted delivery potential to the folate receptor-positive MCF-7 cells. These results suggest that CG5-FU-NPs and FCG5-FU-NPs are promising therapeutic systems for cancer management.

Keywords

5-Fluorouracil Gold nanoparticles Chitosan Folic acid Cytotoxicity 

Notes

Acknowledgements

The authors acknowledge the funding received from the National Research Foundation (NRF) [M Singh-Grant no: 81289], South Africa.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

References

  1. Akinyelu J, Singh M (2018) Chitosan stabilized gold-folate-poly (lactide-co-glycolide) nanoplexes facilitate efficient gene delivery in hepatic and breast cancer cells. J Nanosci Nanotechnol 18:4478–4486CrossRefGoogle Scholar
  2. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC (2014) Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 66:2–25CrossRefGoogle Scholar
  3. Božanić DK, Trandafilović LV, Luyt AS, Djoković V (2010) ‘Green’synthesis and optical properties of silver–chitosan complexes and nanocomposites. React Funct Polym 70:869–873CrossRefGoogle Scholar
  4. Carbinatto FM, de Castro AD, Evangelista RC, Cury BS (2014) Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices. Asian J Pharm Sci 9:27–34CrossRefGoogle Scholar
  5. Chakravarthi SS, Robinson DH (2011) Enhanced cellular association of paclitaxel delivered in chitosan-PLGA particles. Int J Pharm 409:111–120CrossRefGoogle Scholar
  6. Chen B, Le W, Wang Y, Li Z, Wang D, Ren L, Lin L, Cui S, Hu JJ, Hu Y, Yang P (2016) Targeting negative surface charges of cancer cells by multifunctional nanoprobes. Theranostics 11:1887CrossRefGoogle Scholar
  7. Danhier F, Feron O, Préat V (2010) To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release 148:135–146CrossRefGoogle Scholar
  8. Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 67:217–223Google Scholar
  9. Dauthal P, Mukhopadhyay M (2016) Noble metal nanoparticles: plant-mediated synthesis, mechanistic aspects of synthesis, and applications. Ind Eng Chem Res 55:9557–9577CrossRefGoogle Scholar
  10. Devendiran RM et al (2016) Green synthesis of folic acid-conjugated gold nanoparticles with pectin as reducing/stabilizing agent for cancer theranostics. RSC Adv 6:29757–29768CrossRefGoogle Scholar
  11. Dhar S, Reddy EM, Shiras A, Pokharkar V, Prasad BE (2008) Natural gum reduced/stabilized gold nanoparticles for drug delivery formulations chemistry-A. Eur J 14:10244–10250CrossRefGoogle Scholar
  12. Dhas NL, Ige PP, Kudarha RR (2015) Design, optimization and in-vitro study of folic acid conjugated-chitosan functionalized PLGA nanoparticle for delivery of bicalutamide in prostate cancer. Powder Technol 283:234–245CrossRefGoogle Scholar
  13. Haiss W, Thanh NT, Aveyard J, Fernig DG (2007) Determination of size and concentration of gold nanoparticles from UV–Vis. spectra. Anal Chem 79:4215–4221CrossRefGoogle Scholar
  14. Ismail ST, Al-Kotaji MM, Khayrallah AA (2017) Formulation and evaluation of nystatin microparticles as a sustained release system. Iraqi J Pharm Sci 24:1–10Google Scholar
  15. Kang B-S et al (2017) Enhancing the in vitro anticancer activity of albendazole incorporated into chitosan-coated. PLGA Nanoparticles Carbohydr Polym 159:39–47CrossRefGoogle Scholar
  16. Kuksal A, Tiwary AK, Jain NK, Jain S (2006) Formulation and in vitro, in vivo evaluation of extended-release matrix tablet of zidovudine: influence of combination of hydrophilic and hydrophobic matrix formers. AAPS PharmSciTech 7:E1–E9CrossRefGoogle Scholar
  17. Lazarus GG, Singh M (2016) Cationic modified gold nanoparticles show enhanced gene delivery in vitro. Nanotechnol Rev 5:425–434CrossRefGoogle Scholar
  18. Lee SJ, Min HS, Ku SH, Son S, Kwon IC, Kim SH, Kim K (2014) Tumor-targeting glycol chitosan nanoparticles as a platform delivery carrier in cancer diagnosis therapy. Nanomedicine 9:1697–1713CrossRefGoogle Scholar
  19. Madhusudhan A, Reddy GB, Venkatesham M, Veerabhadram G, Kumar DA, Natarajan S, Yang MY, Hu A, Singh SS (2014) Efficient pH dependent drug delivery to target cancer cells by gold nanoparticles capped with carboxymethyl chitosan. Int J Mol Sci 15:8216–8234CrossRefGoogle Scholar
  20. Maiyo F, Moodley R, Singh M (2016) Cytotoxicity, antioxidant and apoptosis studies of quercetin-3-O glucoside and 4-(β-D-glucopyranosyl-1→ 4-α-L-rhamnopyranosyloxy)-benzyl isothiocyanate from Moringa oleifera. Anticancer Agents Med Chem 16:648–656CrossRefGoogle Scholar
  21. Maney V, Singh M (2017) An in vitro assessment of chitosan/bimetallic PtAu nanocomposites as delivery vehicles for doxorubicin. Nanomedicine 12:2625–2640CrossRefGoogle Scholar
  22. Nivethaa E, Dhanavel S, Narayanan V, Vasu CA, Stephen A (2015) An in vitro cytotoxicity study of 5-fluorouracil encapsulated chitosan/gold nanocomposites towards MCF-7 cells. RSC Adv 5:1024–1032CrossRefGoogle Scholar
  23. Ofokansi KC, Adikwu MU, Okore VC (2007) Preparation and evaluation of mucin-gelatin mucoadhesive microspheres for rectal delivery of ceftriaxone sodium. Drug Develop Ind Pharm 33:691–700CrossRefGoogle Scholar
  24. Parker WB, Cheng YC (1990) Metabolism and mechanism of action of 5-fluorouracil. Pharmacol Ther 48:381–395CrossRefGoogle Scholar
  25. Pauliukaite R, Ghica ME, Fatibello-Filho O, Brett CM (2010) Electrochemical impedance studies of chitosan-modified electrodes for application in electrochemical sensors and biosensors. Electrochim Acta 55:6239–6247CrossRefGoogle Scholar
  26. Ritger PL, Peppas NA (1987) A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 5:37–42CrossRefGoogle Scholar
  27. Safwat MA, Soliman GM, Sayed D, Attia MA (2016) Gold nanoparticles enhance 5-fluorouracil anticancer efficacy against colorectal cancer cells. Int J Pharm 513:648–658CrossRefGoogle Scholar
  28. Salar RK, Kumar N (2016) Synthesis and characterization of vincristine loaded folic acid–chitosan conjugated nanoparticles. Res-Effic Technol 2:199–214Google Scholar
  29. Samadian H, Hosseini-Nami S, Kamrava SK, Ghaznavi H, Shakeri-Zadeh A (2016) Folate-conjugated gold nanoparticle as a new nanoplatform for targeted cancer therapy. J Cancer Res Clin Oncol 142:2217–2229CrossRefGoogle Scholar
  30. Singh J, Roychoudhury A, Srivastava M, Solanki PR, Lee DW, Lee SH, Malhotra B (2014) A dual enzyme functionalized nanostructured thulium oxide based interface for biomedical application. Nanoscale 6:1195–1208CrossRefGoogle Scholar
  31. Song H, Su C, Cui W, Zhu B, Liu L, Chen Z, Zhao L (2013) Folic acid-chitosan conjugated nanoparticles for improving tumor-targeted drug delivery. BioMed Res Int 2013:723158Google Scholar
  32. Sood A, Panchagnula R (1998) Drug release evaluation of diltiazem CR preparations International. J Pharm 175:95–107Google Scholar
  33. Steichen SD, Caldorera-Moore M, Peppas NA (2013) A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics European. J Pharm Sci 48:416–427Google Scholar
  34. Tan Q, Chu Y, Bie M, Wang Z, Xu X (2017) Preparation and investigation of amphiphilic block copolymers/fullerene nanocomposites as nanocarriers for Hydrophobic. Drug Mater 10:92Google Scholar
  35. Turkevich J, Stevenson PC, Hillier J (1951) A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 11:55–75CrossRefGoogle Scholar
  36. Udofot O, Affram K, Bridg’ette Israel EA (2015) Cytotoxicity of 5-fluorouracil-loaded pH-sensitive liposomal nanoparticles in colorectal cancer cell lines. Integr Cancer Sci Ther 2:245Google Scholar
  37. Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM (1999) Polymeric systems for controlled drug release. Chem Rev 99:3181–3198CrossRefGoogle Scholar
  38. Upadhyaya L, Singh J, Agarwal V, Pandey A, Verma SP, Das P, Tewari R (2015) Efficient water soluble nanostructured ZnO grafted O-carboxymethyl chitosan/curcumin-nanocomposite for cancer therapy. Process Biochem 50:678–688CrossRefGoogle Scholar
  39. Venkatpurwar V, Shiras A, Pokharkar V (2011) Porphyran capped gold nanoparticles as a novel carrier for delivery of anticancer drug: in vitro cytotoxicity study. Int J Pharm 409:314–320CrossRefGoogle Scholar
  40. Wang C, Shaw LL (2014) On synthesis of Fe2SiO4/SiO2 and Fe2O3/SiO2 composites through sol–gel and solid state reactions. J Sol-gel Sci Technol 72:602–614CrossRefGoogle Scholar
  41. Yang C-L, Chen J-P, Wei K-C, Chen J-Y, Huang C-W, Liao Z-X (2017) Release of doxorubicin by a folate-grafted, chitosan-coated magnetic nanoparticle. Nanomaterials 7:85CrossRefGoogle Scholar
  42. Yassin AEB, Anwer MK, Mowafy HA, El-Bagory IM, Bayomi MA, Alsarra IA (2010) Optimization of 5-flurouracil solid-lipid nanoparticles: a preliminary study to treat colon cancer. Int J Med Sci 7:398CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Non-Viral Gene Delivery Laboratory, Discipline of BiochemistryUniversity of KwaZulu-NatalDurbanSouth Africa

Personalised recommendations