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Folate-conjugated zein/Fe3O4 nanocomplexes for the enhancement of cellular uptake and cytotoxicity of gefitinib

  • Biomaterials
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Abstract

Integrating various functional components into a single nano-platform is an ideal but challenging strategy for cancer therapy. Herein, a facile approach to fabricating multi-targeted nano-drug delivery systems which can be monitored is reported. Superparamagnetic iron oxide nanoparticles (SPIONs) and gefitinib (GEF) were encapsulated into folic acid-conjugated zein (Fa–zein) nanocomplexes (GEF-FSZs) with good dispersity, high GEF loading efficiency and pH-dependent release profile. The uptake of water-insoluble GEF was facilitated by encapsulating GEF into a zein-based nanocomplex, the magnetic responsive property endowed by SPIONs and the conjugation of Fa, which resulted in enhanced toxicity to A549 cells. The endocytosis study indicated that macropinocytosis and clathrin/caveolae-independent endocytosis exerted great influence on the internalization of GEF-FSZs. These results implied that GEF-FSZs could be a promising candidate for controlled and targeted drug delivery.

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References

  1. Parveen S, Misra R, Sahoo SK (2012) Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomed Nanotechnol 8:147–166

    Article  Google Scholar 

  2. Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46:6387–6392

    Google Scholar 

  3. Iyer AK, Khaled G, Fang J, Maeda H (2006) Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov Today 11:812–818

    Article  Google Scholar 

  4. Duan X, Li Y (2013) Physicochemical characteristics of nanoparticles affect circulation, biodistribution, cellular internalization, and trafficking. Small 9:1521–1532

    Article  Google Scholar 

  5. Jia F, Liu X, Li L, Mallapragada S, Narasimhan B, Wang Q (2013) Multifunctional nanoparticles for targeted delivery of immune activating and cancer therapeutic agents. J Control Release 172:1020–1034

    Article  Google Scholar 

  6. Veiseh O, Gunn JW, Zhang M (2010) Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliver Rev 62:284–304

    Article  Google Scholar 

  7. Mahmoudi M, Sant S, Wang B, Laurent S, Sen T (2011) Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy. Adv Drug Deliver Rev 63:24–46

    Article  Google Scholar 

  8. Wang X, Deng A, Cao W et al (2018) Synthesis of chitosan/poly (ethylene glycol)-modified magnetic nanoparticles for antibiotic delivery and their enhanced anti-biofilm activity in the presence of magnetic field. J Mater Sci 53:6433–6449 https://doi.org/10.1007/s10853-018-1998-9

    Article  Google Scholar 

  9. Nosrati H, Adibtabar M, Sharafi A, Danafar H, Kheiri MH (2018) PAMAM-modified citric acid-coated magnetic nanoparticles as pH sensitive biocompatible carrier against human breast cancer cells. Drug Dev Ind Pharm. https://doi.org/10.1080/03639045.2018.1451881

    Google Scholar 

  10. Nosrati H, Rashidi N, Danafar H, Manjili HK (2017) Anticancer activity of tamoxifen loaded tyrosine decorated biocompatible Fe3O4 magnetic nanoparticles against breast cancer cell lines. J Inorg Organomet Polym 28:1178–1186

    Article  Google Scholar 

  11. Xu J, Cui Z, Xu F, Luo Y (2018) Preparation and self-assembly of Au nanoparticles coordinated Fe3O4 graft block copolymer multifunctional nanohybrids with pH, electrochemical and magnetic stimuli responsiveness. J Mater Sci 53:1945–1961. https://doi.org/10.1007/s10853-017-1675-4

    Article  Google Scholar 

  12. Nosrati H, Mojtahedi A, Danafar H, Kheiri HM (2018) Enzymatic stimuli-responsive methotrexate-conjugated magnetic nanoparticles for target delivery to breast cancer cells and release study in lysosomal condition. J Biomed Mater Res A. https://doi.org/10.1002/jbm.a.36364

    Google Scholar 

  13. Nosrati H, Salehiabar M, Davaran S, Danafar H, Manjili HK (2017) Methotrexate-conjugated l-lysine coated iron oxide magnetic nanoparticles for inhibition of MCF-7 breast cancer cells. Drug Dev Ind Pharm 44:886–894

    Article  Google Scholar 

  14. Rastegari B, Karbalaei-Heidari HR, Zeinali S, Sheardown H (2017) The enzyme-sensitive release of prodigiosin grafted β-cyclodextrin and chitosan magnetic nanoparticles as an anticancer drug delivery system: synthesis, characterization and cytotoxicity studies. Colloid Surf B 158:589–601

    Article  Google Scholar 

  15. Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153:198–205

    Article  Google Scholar 

  16. Yang KK, Kong M, Wei YN et al (2013) Folate-modified–chitosan-coated liposomes for tumor-targeted drug delivery. J Mater Sci 48:1717–1728. https://doi.org/10.1007/s10853-012-6930-0

    Article  Google Scholar 

  17. Chávez-García D, Juarez-Moreno K, Campos C, Tejeda E, Alderete J, Hirata G (2018) Cytotoxicity, genotoxicity and uptake detection of folic acid-functionalized green upconversion nanoparticles Y2O3/Er3+, Yb3+ as biolabels for cancer cells. J Mater Sci 53:6665–6680. https://doi.org/10.1007/s10853-017-1946-0

    Article  Google Scholar 

  18. Walters CL, Arend RC, Armstrong DK, Naumann RW, Alvarez RD (2013) Folate and folate receptor alpha antagonists mechanism of action in ovarian cancer. Gynecol Oncol 131:493–498

    Article  Google Scholar 

  19. Pawar H, Surapaneni SK, Tikoo K, Singh C, Burman R, Gill MS, Suresh S (2016) Folic acid functionalized long-circulating co-encapsulated docetaxel and curcumin solid lipid nanoparticles: in vitro evaluation, pharmacokinetic and biodistribution in rats. Drug Deliv 23:1453–1468

    Article  Google Scholar 

  20. Liu G, Pang J, Huang Y, Xie Q, Guan G, Jiang Y (2017) Self-assembled nanospheres of folate-decorated zein for the targeted delivery of 10-hydroxycamptothecin. Ind Eng Chem Res 56:8517–8527

    Article  Google Scholar 

  21. Salehiabar M, Nosrati H, Javani E, Aliakbarzadeh F, Manjili HK, Davaran S, Danafar H (2018) Production of biological nanoparticles from bovine serum albumin as controlled release carrier for curcumin delivery. Int J Biol Macromol 115:83–89. https://doi.org/10.1016/j.ijbiomac.2018.1004.1043

    Article  Google Scholar 

  22. Nosrati H, Salehiabar M, Manjili HK, Danafar H, Davaran S (2018) Preparation of magnetic albumin nanoparticles via a simple and one-pot desolvation and co-precipitation method for medical and pharmaceutical applications. Int J Biol Macromol 108:909–915

    Article  Google Scholar 

  23. Liu G, Wei D, Wang H, Hu Y, Jiang Y (2016) Self-assembly of zein microspheres with controllable particle size and narrow distribution using a novel built-in ultrasonic dialysis process. Chem Eng J 284:1094–1105

    Article  Google Scholar 

  24. Liu G, Li S, Huang Y, Wang H, Jiang Y (2016) Incorporation of 10-hydroxycamptothecin nanocrystals into zein microspheres. Chem Eng Sci 155:405–414

    Article  Google Scholar 

  25. Cheng W, Nie J, Xu L et al (2017) pH-Sensitive delivery vehicle based on folic acid-conjugated polydopamine-modified mesoporous silica nanoparticles for targeted cancer therapy. ACS Appl Mater Interface 9:18462–18473

    Article  Google Scholar 

  26. Cohen MH, Williams GA, Sridhara R et al (2004) United States food and drug administration drug approval summary. Clin Cancer Res 10:1212–1218

    Article  Google Scholar 

  27. Lin M, Lu D, Zhu J, Yang C, Zhang Y, Liu Z (2012) Magnetic enzyme nanogel (MENG): a universal synthetic route for biocatalysts. Chem Commun 48:3315–3317

    Article  Google Scholar 

  28. Gupta AK, Gupta M (2005) Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 26:3995–4021

    Article  Google Scholar 

  29. Vyas A, Saraf S, Saraf S (2010) Encapsulation of cyclodextrin complexed simvastatin in chitosan nanocarriers: a novel technique for oral delivery. J Incl Phenom Macro 66:251–259

    Article  Google Scholar 

  30. Li Y, Li J, Xia Q, Zhang B, Wang Q, Huang Q (2012) Understanding the dissolution of α-zein in aqueous ethanol and acetic acid solutions. J Phys Chem B 116:12057–12064

    Article  Google Scholar 

  31. Sly AC, Taylor J, Taylor JR (2014) Improvement of zein dough characteristics using dilute organic acids. J Cereal Sci 60:157–163

    Article  Google Scholar 

  32. Nosrati H, Sefidi N, Sharafi A, Danafar H, Manjili HK (2018) Bovine serum albumin (BSA) coated iron oxide magnetic nanoparticles as biocompatible carriers for curcumin-anticancer drug. Bioorg Chem 76:501–509

    Article  Google Scholar 

  33. Iversen TG, Skotland T, Sandvig K (2011) Endocytosis and intracellular transport of nanoparticles: present knowledge and need for future studies. Nano Today 6:176–185

    Article  Google Scholar 

  34. Galetti M, Alfieri RR, Cavazzoni A et al (2010) Functional characterization of gefitinib uptake in non-small cell lung cancer cell lines. Biochem Pharmacol 80:179–187

    Article  Google Scholar 

  35. Huth S, Lausier J, Gersting SW, Rudolph C, Plank C, Welsch U, Rosenecker J (2004) Insights into the mechanism of magnetofection using PEI-based magnetofectins for gene transfer. J Gene Med 6:923–936

    Article  Google Scholar 

  36. Liu Q, Zhang J, Xia W, Gu H (2012) Magnetic field enhanced cell uptake efficiency of magnetic silica mesoporous nanoparticles. Nanoscale 4:3415–3421

    Article  Google Scholar 

  37. Yuan H, Miao J, Du Y-Z, You J, Hu F-Q, Zeng S (2008) Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells. Int J Pharm 348:137–145

    Article  Google Scholar 

  38. Chang Y, Li Y, Meng X, Liu N, Sun D, Liu H, Wang J (2013) Dendrimer functionalized water soluble magnetic iron oxide conjugates as dual imaging probe for tumor targeting and drug delivery. Polym Chem 4:789–794

    Article  Google Scholar 

  39. Jones SK, Sarkar A, Feldmann DP, Hoffmann P, Merkel O (2017) Revisiting the value of competition assays in folate receptor-mediated drug delivery. Biomaterials 75:1420–1426

    Google Scholar 

  40. Jones SK, Lizzio V, Merkel OM (2015) Folate receptor targeted delivery of siRNA and paclitaxel to ovarian cancer cells via folate conjugated triblock copolymer to overcome TLR4 driven chemotherapy resistance. Biomacromolecules 17:76–87

    Article  Google Scholar 

  41. Zou T, Gu L (2013) TPGS emulsified zein nanoparticles enhanced oral bioavailability of daidzin: in vitro characteristics and in vivo performance. Mol Pharm 10:2062–2070

    Article  Google Scholar 

  42. Wang H, Cao Y, Wang C, Cui S, Mi L, Miyazawa T (2016) Green self-assembly of zein-conjugated ZnO/Cd (OH) Cl hierarchical nanocomposites with high cytotoxicity and immune organs targeting. Sci Rep 6:24387. https://doi.org/10.1038/srep24387

    Article  Google Scholar 

  43. Delenclos M, Trendafilova T, Mahesh D, Baine AM, Moussaud S, Yan IK, Patel T, McLean PJ (2017) Investigation of endocytic pathways for the internalization of exosome-associated oligomeric alpha-synuclein. Front Neurosci 11:172. https://doi.org/10.3389/fnins.2017.00172

    Article  Google Scholar 

  44. Silva E, Barreiros L, Segundo MA, Lima SAC, Reis S (2017) Cellular interactions of a lipid-based nanocarrier model with human keratinocytes: unravelling transport mechanisms. Acta Biomater 53:439–449

    Article  Google Scholar 

  45. Xu S, Olenyuk BZ, Okamoto CT, Hamm-Alvarez SF (2013) Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances. Adv Drug Deliver Rev 65:121–138

    Article  Google Scholar 

  46. Yang T, Xu L, Li B et al (2017) Antitumor activity of a folate receptor-targeted immunoglobulin g-doxorubicin conjugate. Int J Nanomed 12:2505–2515

    Article  Google Scholar 

  47. Behzadi S, Serpooshan V, Tao W et al (2017) Cellular uptake of nanoparticles: journey inside the cell. Chem Soc Rev 46:4218–4244

    Article  Google Scholar 

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Nos. 21476086, 21776102, 21706079) and the Fundamental Research Funds for the Central Universities (No. 2017BQ060).

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, China

    Jiafeng Pang, Zhixian Li, Shaomin Li, Hongdi Wang & Yanbin Jiang

  2. College of Life Science and Technology, Jinan University, Guangzhou, 510632, China

    Shuying Lin & Qiuling Xie

  3. National Engineering Research Centre of Genetic Medicine, Guangzhou, 510632, China

    Qiuling Xie

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  1. Jiafeng Pang
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  3. Shaomin Li
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Correspondence to Zhixian Li or Qiuling Xie.

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Pang, J., Li, Z., Li, S. et al. Folate-conjugated zein/Fe3O4 nanocomplexes for the enhancement of cellular uptake and cytotoxicity of gefitinib. J Mater Sci 53, 14907–14921 (2018). https://doi.org/10.1007/s10853-018-2684-7

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