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Polymeric nanoparticles tryptophan-graft-p(HEMA): a study on synthesis, characterization, and toxicity

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Abstract

Poly-hydroxyethyl methacrylate [p(HEMA)] is one of the most widely used polymers in different biomedical applications because it is a biocompatible and a biodegradable material. Tryptophan (Trp) is a biocompatible, antioxidant, and anti-inflammatory amino acid. Trp modification contributes to the more effective use of nanoparticles in cancer therapy. The aim of this study was to synthesize polymeric nanoparticles tryptophan-graft-poly(HEMA) [Trp-g-p(HEMA)] and assess characterization and toxicity/biocompatibility potential of it in terms of using a drug carrier. The nanoparticles were synthesized with surfactant-free emulsion polymerization and grafting technique and the grafting efficiency was found as 78.65 ± 2.48%. The characterization of the nanoparticles was performed by FT-IR spectroscopy, zeta analysis, scanning electron microscopy, atomic force microscopy, and swelling test. The nanopolymers had the spectra from 750 to 4000 cm−1 and characteristic peaks of stretching bands, 164.1 ± 29.2 nm average size, − 10.2 ± 8.7 mV surface charge, smooth surface, and nearly spherical shape. The swelling ratios of them were estimated as 79.52 ± 0.86% in d.w. and 93.33 ± 2.32% in PBS at 25 °C, 35.71 ± 0.62% in d.w., and 42.86 ± 0.64% in PBS at 37 °C. The nanoparticles did not induce cytotoxicity, oxidative stress generation, and genotoxicity on human healthy lymphocyte cells. Trp-g-p(HEMA) had hemocompatible properties. We found no irritant effect in the HET-CAM test. The acute oral LD50 value of the nanopolymers was > 2000 mg/kg body weight on BALB/c mice. We announce that the polymeric nanoparticles Trp-g-p(HEMA) is a biocompatible material and has potential to use as a drug carrier for oral, intravenous, and ocular administrations.

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References

  1. Chen G, Roy I, Yang C, Prasad PN (2016) Nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy. Chem Rev. https://doi.org/10.1021/acs.chemrev.5b00148

    Article  PubMed  PubMed Central  Google Scholar 

  2. Wang AZ, Langer R, Farokhzad OC (2012) Nanoparticle delivery of cancer drugs. Annu Rev Med. https://doi.org/10.1146/annurev-med-040210-162544

    Article  PubMed  Google Scholar 

  3. Calzoni E, Cesaretti A, Polchi A, Di Michele A, Tancini B, Emiliani C (2019) Biocompatible polymer nanoparticles for drug delivery applications in cancer and neurodegenerative disorder therapies. J Funct Biomater. https://doi.org/10.3390/jfb10010004

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bennet D, Kim S (2014) Polymer nanoparticles for smart drug delivery. In: Sezer AD (ed) Application of nanotechnology in drug delivery. InTech, Croatia, pp 257–309. https://doi.org/10.5772/58422

    Chapter  Google Scholar 

  5. Akagi T, Higashi M, Kaneko T, Kida T, Akashi M (2006) Hydrolytic and enzymatic degradation of nanoparticles based on amphiphilic poly(γ-glutamic acid)-graft-l-phenylalanine copolymers. Biomacromol. https://doi.org/10.1021/bm050657i

    Article  Google Scholar 

  6. Yu MK, Park J, Jon S (2012) Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy. Theranostics. https://doi.org/10.7150/thno.3463

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wu J, Deng C, Meng F, Zhang J, Sun H, Zhong Z (2017) Hyaluronic acid coated PLGA nanoparticulate docetaxel effectively targets and suppresses orthotopic human lung cancer. J Control Release. https://doi.org/10.1016/j.jconrel.2016.12.024

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sukhanova A, Bozrova S, Sokolov P, Berestovoy M, Karaulov A, Nabiev I (2018) Dependence of nanoparticle toxicity on their physical and chemical properties. Nanoscale Res Lett. https://doi.org/10.1186/s11671-018-2457-x

    Article  PubMed  PubMed Central  Google Scholar 

  9. Peppas NA, Hilt JZ, Khademhosseini A, Langer R (2006) Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv Mater. https://doi.org/10.1002/adma.200501612

    Article  Google Scholar 

  10. Li CC, Chauhan A (2007) Ocular transport model for ophthalmic delivery of timolol through p-HEMA contact lenses. J Drug Deliv Sci Technol. https://doi.org/10.1016/S1773-2247(07)50010-9

    Article  Google Scholar 

  11. Curcio M, Cirillo G, Parisi OI, Iemma F, Spizzirri UG, Altimari I et al (2011) Poly(2-hydroxyethyl methacrylate)-quercetin conjugate as biomaterial in ophthalmology: an “ab initio” study. J Funct Biomater. https://doi.org/10.3390/jfb2010001

    Article  PubMed  PubMed Central  Google Scholar 

  12. Johnson RP, Jeong YI, Choi E, Chung CW, Kang DH, Oh SO, Suh H, Kim I (2012) Biocompatible poly(2-hydroxyethyl methacrylate)-b-poly(L-histidine) hybrid materials for ph-sensitive intracellular anticancer drug delivery. Adv Funct Mater. https://doi.org/10.1002/adfm.201102756

    Article  Google Scholar 

  13. Davaran S, Fazeli H, Ghamkhari A, Rahimi F, Molavi O, Anzabi M, Salehi R (2018) Synthesis and characterization of novel P(HEMA-LAMADQUAT) micelles for co-delivery of methotrexate and Chrysin in combination cancer chemotherapy. J Biomater Sci Polym Ed. https://doi.org/10.1080/09205063.2018.1456026

    Article  PubMed  Google Scholar 

  14. Bakan B, Kayhan CT, Karayildirim CK, Dagdeviren M, Gulcemal S, Yildirim Y, Akgol S, Yavasoglu NUK (2019) Synthesis, characterization, toxicity and in vivo imaging of lysine graft polymeric nanoparticles. J Polym Res. https://doi.org/10.1007/s10965-019-1901-7

    Article  Google Scholar 

  15. Bakan B, Gülcemal S, Akgöl S, Hoet PH, Yavaşoğlu NÜK (2020) Synthesis, characterization and toxicity assessment of a new polymeric nanoparticle, l-glutamic acid-gp(HEMA). Chem Biol Interact. https://doi.org/10.1016/j.cbi.2019.108870

    Article  PubMed  Google Scholar 

  16. Avcıbaşı U, Türkyarar T, Karadağ A, Bakan B, Yavaşoğlu NÜK, Kuşat K et al (2021) Preparation of a 99mTc-labeled graft polymer and its in vitro and in vivo evaluation. J Radioanal Nucl Chem. https://doi.org/10.1007/s10967-021-07817-6

    Article  Google Scholar 

  17. Nayak BN, Buttar HS (2016) Evaluation of the antioxidant properties of tryptophan and its metabolites in in vitro assay. J Complement Integr. https://doi.org/10.1515/jcim-2015-0051

    Article  Google Scholar 

  18. Kim DY, Kim M, Shinde S, Saratale RG, Sung JS, Ghodake G (2017) Temperature dependent synthesis of tryptophan-functionalized gold nanoparticles and their application in imaging human neuronal cells. ACS Sustain Chem Eng. https://doi.org/10.1021/acssuschemeng.7b01101

    Article  Google Scholar 

  19. Qiao M, Liu X, Song JW, Yang T, Chen ML, Wang JH (2018) Improving the adsorption capacity for ovalbumin by functional modification of aminated mesoporous silica nanoparticles with tryptophan. J Mater Chem B. https://doi.org/10.1039/C8TB02221F

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gong QJ, Han HX, Wang YD, Yao CZ, Yang HY, Qiao JL (2020) An electrochemical sensor for dopamine detection based on the electrode of a poly-tryptophan-functionalized graphene composite. New Carbon Mater. https://doi.org/10.1016/S1872-5805(20)60473-5

    Article  Google Scholar 

  21. Roy SG, Acharya R, Chatterji U, De P (2013) RAFT polymerization of methacrylates containing a tryptophan moiety: controlled synthesis of biocompatible fluorescent cationic chiral polymers with smart pH-responsiveness. Polym Chem. https://doi.org/10.1039/C2PY20821K

    Article  PubMed Central  Google Scholar 

  22. Prendergast GC (2011) Why tumours eat tryptophan. Nature. https://doi.org/10.1038/478192a

    Article  PubMed  Google Scholar 

  23. Ghanbari N, Salehi Z, Khodadadi AA, Shokrgozar MA, Saboury AA, Farzaneh F (2021) Tryptophan-functionalized graphene quantum dots with enhanced curcumin loading capacity and pH-sensitive release. J Drug Deliv Sci Technol. https://doi.org/10.1016/j.jddst.2020.102137

    Article  Google Scholar 

  24. Türkcan C, Akgöl S, Denizli A (2013) Silanized polymeric nanoparticles for DNA isolation. Mater Sci Eng C. https://doi.org/10.1016/j.msec.2013.05.015

    Article  Google Scholar 

  25. Akgöl S, Kaçar Y, Özkara S, Yavuz H, Denizli A, Arica MY (2001) Immobilization of catalase via adsorption onto L-histidine grafted functional pHEMA based membrane. J Mol Catal B Enzym. https://doi.org/10.1016/S1381-1177(01)00029-7

    Article  Google Scholar 

  26. Pathania D, Sharma R (2012) Synthesis and characterization of graft copolymers of methacrylic acid onto gelatinized potato starch using chromic acid initiator in presence of air. Adv Mat Lett 3:136–142

    Article  Google Scholar 

  27. Yin J, Dai Z, Yan S, Cao T, Ma J, Chen X (2007) Polyelectrolyte complexes based on chitosan and poly(L-glutamic acid). Polym Int. https://doi.org/10.1002/pi.2247

    Article  Google Scholar 

  28. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  PubMed  Google Scholar 

  29. Güner A, Türkez H, Aslan A (2012) The in vitro effects of Dermotocarpon intestiniforme (a lichen) extracts against cadmium induced genetic and oxidative damage. Ekoloji. https://doi.org/10.5053/ekoloji.2012.845

    Article  Google Scholar 

  30. Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem. https://doi.org/10.1016/j.clinbiochem.2005.08.008

    Article  PubMed  Google Scholar 

  31. Evans HJ, O’Riordan ML (1975) Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. Mutat Res. https://doi.org/10.1016/0165-1161(75)90082-5

    Article  PubMed  Google Scholar 

  32. Fenech M, Morley AA (1985) Measurement of micronuclei in lymphocytes. Mutat Res. https://doi.org/10.1016/0165-1161(85)90015-9

    Article  PubMed  Google Scholar 

  33. Fenech M, Chang WP, Kirsch-Volders M, Holland N, Bonassi S, Zeiger E (2003) HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res. https://doi.org/10.1016/S1383-5718(02)00249-8

    Article  PubMed  Google Scholar 

  34. Parnham MJ, Wetzig H (1993) Toxicity screening of liposomes. Chem Phys Lipids. https://doi.org/10.1016/0009-3084(93)90070-J

    Article  PubMed  Google Scholar 

  35. Lin YS, Haynes CL (2010) Impacts of mesoporous silica nanoparticle size, pore ordering, and pore integrity on hemolytic activity. J Am Chem Soc. https://doi.org/10.1021/ja910846q

    Article  PubMed  PubMed Central  Google Scholar 

  36. ICCVAM Test Method Evaluation Report (2010) Current validation status of in vitro test methods proposed for identifying eye injury hazard potential of chemicals and products” NIH Publication No. 10-7553. https://ntp.niehs.nih.gov/iccvam/docs/ocutox_docs/invitro-2010/tmer-vol1.pdf

  37. OECD Guidelines For The Testing Of Chemicals No. 425 (2008) Acute Oral Toxicity—Up-and-Down-Procedure (UDP)

  38. Khalid M, El-Sawy HS (2017) Polymeric nanoparticles: promising platform for drug delivery. Int J Pharm. https://doi.org/10.1016/j.ijpharm.2017.06.052

    Article  PubMed  Google Scholar 

  39. Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. https://doi.org/10.1021/mp800051m

    Article  PubMed  PubMed Central  Google Scholar 

  40. Owens DE III, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. https://doi.org/10.1016/j.ijpharm.2005.10.010

    Article  PubMed  Google Scholar 

  41. He C, Hu Y, Yin L, Tang C, Yin C (2010) Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials. https://doi.org/10.1016/j.biomaterials.2010.01.065

    Article  PubMed  PubMed Central  Google Scholar 

  42. Win KY, Feng SS (2005) Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials. https://doi.org/10.1016/j.biomaterials.2004.07.050

    Article  PubMed  Google Scholar 

  43. Karlsson J, Vaughan HJ, Green JJ (2018) Biodegradable polymeric nanoparticles for therapeutic cancer treatments. Annu Rev Chem Biomol Eng. https://doi.org/10.1146/annurev-chembioeng-060817-084055

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lambert G, Bertrand JR, Fattal E, Subra F, Pinto-Alphandary H, Malvy C, Auclair C, Couvreur P (2000) EWS Fli-1 antisense nanocapsules inhibits ewing sarcoma-related tumor in mice. Biochem Biophys Res Commun. https://doi.org/10.1006/bbrc.2000.3963

    Article  PubMed  Google Scholar 

  45. Bootz A, Vogel V, Schubert D, Kreuter J (2004) Comparison of scanning electron microscopy, dynamic light scattering and analytical ultracentrifugation for the sizing of poly(butyl cyanoacrylate) nanoparticles. Eur J Pharm Biopharm. https://doi.org/10.1016/S0939-6411(03)00193-0

    Article  PubMed  Google Scholar 

  46. Domingos RF, Baalousha MA, Ju-Nam Y, Reid MM, Tufenkji N, Lead JR, Leppard GG, Wilkinson KJ (2009) Characterizing manufactured nanoparticles in the environment multimethod determination of particle sizes. Environ Sci Technol. https://doi.org/10.1021/es900249m

    Article  PubMed  Google Scholar 

  47. Eaton P, Quaresma P, Soares C, Neves C, De Almeida MP, Pereira E, West P (2017) A direct comparison of experimental methods to measure dimensions of synthetic nanoparticles. Ultramicroscopy. https://doi.org/10.1016/j.ultramic.2017.07.001

    Article  PubMed  Google Scholar 

  48. Ganji F, Vasheghani FS, Vasheghani FE (2010) Theoretical description of hydrogel swelling: a review. Iran Polym J 19:375–398

    CAS  Google Scholar 

  49. Bajpai AK, Likhitkar S (2013) Investigation of magnetically enhanced swelling behaviour of superparamagnetic starch nanoparticles. Bull Mater Sci 36(1):15–24

    Article  CAS  Google Scholar 

  50. Gupta MK, Bajpai J, Bajpai AK (2014) The biocompatibility and water uptake behavior of superparamagnetic poly(2-Hydroxyethyl methacrylate)–magnetite nanocomposites as possible nanocarriers for magnetically mediated drug delivery system. J Polym Res. https://doi.org/10.1007/s10965-014-0518-0

    Article  Google Scholar 

  51. Kumar PS, Abhilash S, Manzoor K, Nair SV, Tamura H, Jayakumar R (2010) Preparation and characterization of novel β-chitin/nanosilver composite scaffolds for wound dressing applications. Carbohydr Polym. https://doi.org/10.1016/j.carbpol.2009.12.024

    Article  Google Scholar 

  52. Dobić SN, Filipović JM, Tomić SL (2012) Synthesis and characterization of poly(2-hydroxyethyl methacrylate/itaconic acid/poly(ethylene glycol) dimethacrylate) hydrogels. Chem Eng J. https://doi.org/10.1016/j.cej.2011.10.083

    Article  Google Scholar 

  53. Chouhan R, Bajpai AK (2009) Magnetically guided release of ciprofloxacin from superparamagnetic polymer nanocomposites. J Mater Sci Mater Med. https://doi.org/10.1163/092050610X496387

    Article  PubMed  Google Scholar 

  54. Manke A, Wang L, Rojanasakul Y (2013) Mechanisms of nanoparticle-induced oxidative stress and toxicity. Biomed Res Int. https://doi.org/10.1155/2013/942916

    Article  PubMed  PubMed Central  Google Scholar 

  55. Singh N, Manshian B, Jenkins GJ, Griffiths SM, Williams PM, Maffeis TG, Wright CJ, Doak SH (2009) NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. Biomaterials. https://doi.org/10.1016/j.biomaterials.2009.04.009

    Article  PubMed  PubMed Central  Google Scholar 

  56. Magdolenova Z, Collins A, Kumar A, Dhawan A, Stone V, Dusinska M (2014) Mechanisms of genotoxicity. A review of in vitro and in vivo studies with engineered nanoparticles. Nanotoxicology. https://doi.org/10.3109/17435390.2013.773464

    Article  PubMed  Google Scholar 

  57. Adabi M, Naghibzadeh M, Adabi M, Zarrinfard MA, Esnaashari SS, Seifalian AM et al (2017) Biocompatibility and nanostructured materials: applications in nanomedicine. Artif Cells Nanomed Biotechnol. https://doi.org/10.1080/21691401.2016.1178134

    Article  PubMed  Google Scholar 

  58. Zhang Y, Chu D, Zheng M, Kissel T, Agarwal S (2012) Biocompatible and degradable poly(2-hydroxyethyl methacrylate) based polymers for biomedical applications. Polym Chem. https://doi.org/10.1039/C2PY20403G

    Article  Google Scholar 

  59. Bayramoğlu G, Yılmaz M, Batislam E, Arıca MY (2008) Heparin-coated poly (hydroxyethyl methacrylate/albumin) hydrogel networks: In vitro hemocompatibility evaluation for vascular biomaterials. J Appl Polym Sci. https://doi.org/10.1002/app.28062

    Article  Google Scholar 

  60. De La Harpe KM, Kondiah PPD, Choonara YE, Marimuthu T, Du Toit LC, Pillay V (2019) The hemocompatibility of nanoparticles: a review of cell–nanoparticle interactions and hemostasis. Cells. https://doi.org/10.3390/cells8101209

    Article  PubMed  PubMed Central  Google Scholar 

  61. Chenthamara D, Subramaniam S, Ramakrishnan SG, Krishnaswamy S, Essa MM, Lin FH, Qoronfleh MW (2019) Therapeutic efficacy of nanoparticles and routes of administration. Biomater Res. https://doi.org/10.1186/s40824-019-0166-x

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Characterization analysis and experimental studies were performed in Ege University, Drug Research and Development and Pharmacokinetic Applications (ARGEFAR). The authors thank Biorege Lab. for contributions to synthesis of the nanoparticles.

Funding

This study was supported by Ege University, Scientific Research Project (Project Number is 2017/FEN/028).

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Authors and Affiliations

  1. Faculty of Science, Department of Biology, Ege University, 35100, Bornova, Izmir, Turkey

    Cem Guler & N. Ulku Karabay Yavasoglu

  2. Faculty of Science, Department of Chemistry, Ege University, 35100, Izmir, Turkey

    Suleyman Gulcemal

  3. Faculty of Health Sciences, Department of Occupational Health and Safety, Sinop University, Sinop, Turkey

    Adem Guner

  4. Faculty of Science, Department of Biochemistry, Ege University, 35100, Izmir, Turkey

    Sinan Akgol

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  1. Cem Guler
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Guler, C., Gulcemal, S., Guner, A. et al. Polymeric nanoparticles tryptophan-graft-p(HEMA): a study on synthesis, characterization, and toxicity. Polym. Bull. 80, 10973–10996 (2023). https://doi.org/10.1007/s00289-022-04607-2

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