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The effect of a novel drug delivery system using encapsulated antimicrobial peptide Protonectin (IL-12) into Nano micelle PEG-PCL on A549 adenocarcinoma lung cell line

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Abstract

In this study, the effect of protonectin as an antimicrobial peptide in its encapsulated form into PEG-PCL Nano micelle on bioability of human cancer lung of A549 was investigated. By applying 12 µg/ml and 50 µg/ml of the peptide in its encapsulated form and post 24 h and 48 h cell treatment, highest cytotoxicity on A549 was noticed. Biodegradable and biocompatible micelles were made by connecting poly (ethylene glycol) and poly (Ɛ-caprolactone) (PEG-PCL). NMR and FT-IR techniques were applied to characterize PEG-PCL micelle, while the properties of encapsulated peptide into PEG-PCL were further researched by using HPLC, scanning electron microscope (SEM), dynamic light scattering (DLS) as well as zeta potential. The impacts of PEG-PCL encapsulated protonectin with yield loading of 89.7% on the gene expression pattern of metastatic factors BMI-1 and CD44 were examined by the real-time RT PCR. Outcomes exhibited that BMI1 gene expression was down-regulated at a higher level compared to that of CD44 at the concentration of 12 µg/ml, and post 24 and 48 h. In conclusion, our finding supports a novel drug delivery system that can be applicable to enhance the solubility of insoluble drugs, has harmless effects on cancer cells on its own, and is cytotoxic in its encapsulated form.

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References

  1. Sori WJ, Feng J, Godana AW et al (2021) DFD-Net: lung cancer detection from denoised CT scan image using deep learning. Front Comput Sci. https://doi.org/10.1007/s11704-020-9050-z

    Article  Google Scholar 

  2. Ahmad MZ, Alkahtani SA, Akhter S et al (2016) Progress in nanotechnology-based drug carrier in designing of curcumin nanomedicines for cancer therapy: Current state-of-the-art. J Drug Target 24:273–293. https://doi.org/10.3109/1061186X.2015.1055570

    Article  CAS  PubMed  Google Scholar 

  3. Huang X, Huang J, Leng D et al (2017) Gefitinib-loaded DSPE-PEG2000 nanomicelles with CD133 aptamers target lung cancer stem cells. World J Surg Oncol 15:1–10. https://doi.org/10.1186/s12957-017-1230-4

    Article  Google Scholar 

  4. Litman T, Druley TE, Stein WD, Bates SE (2001) From MDR to MXR: New understanding of multidrug resistance systems, their properties and clinical significance. Cell Mol Life Sci 58:931–959. https://doi.org/10.1007/PL00000912

    Article  CAS  PubMed  Google Scholar 

  5. Boehm T, Folkman J, Browder T, O’Reilly MS (1997) Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390:404–407. https://doi.org/10.1038/37126

    Article  CAS  PubMed  Google Scholar 

  6. Zeng X, Morgenstern R, Nyström AM (2014) Nanoparticle-directed sub-cellular localization of doxorubicin and the sensitization breast cancer cells by circumventing GST-Mediated drug resistance. Biomaterials 35:1227–1239. https://doi.org/10.1016/j.biomaterials.2013.10.042

    Article  CAS  PubMed  Google Scholar 

  7. Kapse-Mistry S, Govender T, Srivastava R, Yergeri M (2014) Nanodrug delivery in reversing multidrug resistance in cancer cells. Front Pharmacol 5:159. https://doi.org/10.3389/fphar.2014.00159

  8. Wei Z, Hao J, Yuan S et al (2009) Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: Formulation, optimization and in vitro characterization. Int J Pharm 376:176–185. https://doi.org/10.1016/j.ijpharm.2009.04.030

    Article  CAS  PubMed  Google Scholar 

  9. Owens DE, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102. https://doi.org/10.1016/j.ijpharm.2005.10.010

    Article  CAS  PubMed  Google Scholar 

  10. Cambón A, Rey-Rico A, Mistry D et al (2013) Doxorubicin-loaded micelles of reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers as efficient “active” chemotherapeutic agents. Int J Pharm 445:47–57. https://doi.org/10.1016/j.ijpharm.2013.01.056

    Article  CAS  PubMed  Google Scholar 

  11. Ahmed MS, Dutta RK, Manandhar P et al (2019) A guanylurea-functionalized conjugated polymer enables RNA interference in ex vivo human airway epithelium. Chem Commun 55:7804–7807. https://doi.org/10.1039/c9cc02856k

  12. Thundimadathil J (2012) Cancer treatment using peptides: current therapies and future prospects. J Amino Acids 2012:1–13. https://doi.org/10.1155/2012/967347

    Article  CAS  Google Scholar 

  13. Scheberl A, Khalil ML, Maghsoodi F et al (2020) Quantitative determination of dark and light-activated antimicrobial activity of poly (phenylene ethynylene), polythiophene, and oligo (phenylene ethynylene) electrolytes. ACS Appl Mater Interfaces 12:21322–21329. https://doi.org/10.1021/acsami.0c02939

    Article  CAS  PubMed  Google Scholar 

  14. Wang K, Dang W, Yan J et al (2013) Membrane perturbation action mode and structure-activity relationships of protonectin, a novel antimicrobial peptide from the venom of the neotropical social wasp Agelaia pallipes pallipes. Antimicrob Agents Chemother 57:4632–4639. https://doi.org/10.1128/AAC.02311-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang K, Dang W, Xie J et al (2015) Antimicrobial peptide protonectin disturbs the membrane integrity and induces ROS production in yeast cells. Biochim Biophys Acta - Biomembr 1848:2365–2373. https://doi.org/10.1016/j.bbamem.2015.07.008

    Article  CAS  Google Scholar 

  16. Baptista-Saidemberg NB, Saidemberg DM, de Souza BM et al (2010) Protonectin (1–6): A novel chemotactic peptide from the venom of the social wasp Agelaia pallipes pallipes. Toxicon 56:880–889. https://doi.org/10.1016/j.toxicon.2010.06.011

    Article  CAS  PubMed  Google Scholar 

  17. Kutlehria S, Behl G, Patel K et al (2018) Cholecalciferol-PEG conjugate based nanomicelles of doxorubicin for treatment of triple-negative breast cancer. AAPS PharmSciTech 19:792–802. https://doi.org/10.1208/s12249-017-0885-z

    Article  CAS  PubMed  Google Scholar 

  18. Mousavi SD, Maghsoodi F, Panahandeh F et al (2018) Doxorubicin delivery via magnetic nanomicelles comprising from reduction-responsive poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-SS-PCL) and loaded with superparamagnetic iron oxide (SPIO) nanoparticles: Preparation, characterization and simulation. Mater Sci Eng C 92:631–643. https://doi.org/10.1016/j.msec.2018.06.066

    Article  CAS  Google Scholar 

  19. Moon JH, Manandhar P, Torabi H et al (2019) Phenyleneethynylene trimer-based rigid-flexible [2+2] macrocycles for nucleic acid labelling in live cells. Chem Commun 55:5930–5933. https://doi.org/10.1039/c9cc02162k

    Article  CAS  Google Scholar 

  20. Kataoka K, Harada A, Nagasaki Y (2012) Block copolymer micelles for drug delivery: Design, characterization and biological significance. Adv Drug Deliv Rev 64:37–48. https://doi.org/10.1016/j.addr.2012.09.013

    Article  Google Scholar 

  21. Oh KT, Bronich TK, Kabanov AV (2004) Micellar formulations for drug delivery based on mixtures of hydrophobic and hydrophilic Pluronic® block copolymers. J Control Release 94:411–422. https://doi.org/10.1016/j.jconrel.2003.10.018

    Article  CAS  PubMed  Google Scholar 

  22. Mansour HM, Sohn MJ, Al-Ghananeem A, DeLuca PP (2010) Materials for pharmaceutical dosage forms: Molecular pharmaceutics and controlled release drug delivery aspects. Int J Mol Sci 11:3298–3322. https://doi.org/10.3390/ijms11093298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Torabi H, Ramazani SaadatAbadi A (2019) Property Investigation of Poly (Ethylene Co-vinyl Acetate)/Poly (l-Lactic Acid)/Organo Clay Nanocomposites. J Polym Environ 27:2886–2894. https://doi.org/10.1007/s10924-019-01558-0

    Article  CAS  Google Scholar 

  24. Xiong XY, Tam KC, Gan LH (2003) Synthesis and aggregation behavior of pluronic F127/poly(lactic acid) block copolymers in aqueous solutions. Macromolecules 36:9979–9985. https://doi.org/10.1021/ma035292d

    Article  CAS  Google Scholar 

  25. Dalhaimer P, Engler AJ, Parthasarathy R, Discher DE (2004) Targeted worm micelles. Biomacromol 5:1714–1719. https://doi.org/10.1021/bm049884v

    Article  CAS  Google Scholar 

  26. Talelli M, Barz M, Rijcken CJF et al (2015) Core-crosslinked polymeric micelles: Principles, preparation, biomedical applications and clinical translation. Nano Today 10:93–117. https://doi.org/10.1016/j.nantod.2015.01.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Eskandari R, Asoodeh A, Behnam-Rassouli F (2020) The Therapeutic Effects of an Antimicrobial Peptide Protonectin (IL-12) on A549 Cancer Cell Line. Int J Pept Res Ther. https://doi.org/10.1007/s10989-020-10116-5

    Article  Google Scholar 

  28. Danafar H (2016) MPEG–PCL copolymeric nanoparticles in drug delivery systems. Cogent Med 3:1142411. https://doi.org/10.1080/2331205x.2016.1142411

    Article  Google Scholar 

  29. Han X, Liu J, Liu M et al (2009) 9-NC-loaded folate-conjugated polymer micelles as tumor targeted drug delivery system: Preparation and evaluation in vitro. Int J Pharm 372:125–131. https://doi.org/10.1016/j.ijpharm.2008.12.035

    Article  CAS  PubMed  Google Scholar 

  30. MohseniBandpi A, Eslami A, Shahsavani A et al (2017) Physicochemical characterization of ambient PM2.5 in Tehran air and its potential cytotoxicity in human lung epithelial cells (A549). Sci Total Environ 593–594:182–190. https://doi.org/10.1016/j.scitotenv.2017.03.150

    Article  CAS  PubMed  Google Scholar 

  31. Li YL, Ye F, Hu Y et al (2009) Identification of suitable reference genes for gene expression studies of human serous ovarian cancer by real-time polymerase chain reaction. Anal Biochem 394:110–116. https://doi.org/10.1016/j.ab.2009.07.022

    Article  CAS  PubMed  Google Scholar 

  32. Qindeel M, Ahmed N, Shah KU et al (2020) New, environment friendly approach for synthesis of amphiphilic PCL–PEG–PCL triblock copolymer: an efficient carrier for fabrication of nanomicelles. J Polym Environ 28:1237–1251. https://doi.org/10.1007/s10924-020-01683-1

    Article  CAS  Google Scholar 

  33. Dela CS, Cruz LT, Tanoue and RAM, (2011) Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med. https://doi.org/10.1016/j.ccm.2011.09.001.Lung

    Article  Google Scholar 

  34. Wu D, Gao Y, Qi Y et al (2014) Peptide-based cancer therapy: Opportunity and challenge. Cancer Lett 351:13–22. https://doi.org/10.1016/j.canlet.2014.05.002

    Article  CAS  PubMed  Google Scholar 

  35. Fu S, Xu X, Ma Y et al (2019) RGD peptide-based non-viral gene delivery vectors targeting integrin αvβ3 for cancer therapy. J Drug Target 27:1–11. https://doi.org/10.1080/1061186X.2018.1455841

    Article  CAS  PubMed  Google Scholar 

  36. Choi KE, Hwang CJ, Gu SM et al (2014) Cancer cell growth inhibitory effect of bee venom via increase of death receptor 3 expression and inactivation of NF-kappa B in NSCLC cells. Toxins (Basel) 6:2210–2228. https://doi.org/10.3390/toxins6082210

    Article  CAS  Google Scholar 

  37. Alami-Milani M, Zakeri-Milani P, Valizadeh H et al (2018) Preparation and evaluation of PCL-PEG-PCL micelles as potential nanocarriers for ocular delivery of dexamethasone. Iran J Basic Med Sci 21:153–164. https://doi.org/10.22038/IJBMS.2017.26590.6513

  38. Yuan X, Xie Q, Su K et al (2017) Systemic delivery of the anticancer agent arenobufagin using polymeric nanomicelles. Int J Nanomedicine 12:4981–4989. https://doi.org/10.2147/IJN.S139128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhou Y, Wen H, Gu L et al (2017) Aminoglucose-functionalized, redox-responsive polymer nanomicelles for overcoming chemoresistance in lung cancer cells. J Nanobiotechnology 15:1–17. https://doi.org/10.1186/s12951-017-0316-z

    Article  CAS  Google Scholar 

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Acknowledgements

The authors appreciate the support provided by Research and Technology Council of the Ferdowsi University of Mashhad, Iran (Grant number: 3/38464, 1394/07/20).

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Rosa Eskandari & Ahmad Asoodeh

  2. Cellular and Molecular Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

    Ahmad Asoodeh

  3. Department of Chemistry, University of North Dakota, 151 Cornell Street Stop 9024, Grand Forks, ND, 58202, USA

    Seyed-Danial Mousavi

  4. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed-Danial Mousavi & Zohreh Firouzi

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  1. Rosa Eskandari
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  4. Zohreh Firouzi
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Correspondence to Ahmad Asoodeh.

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Eskandari, R., Asoodeh, A., Mousavi, SD. et al. The effect of a novel drug delivery system using encapsulated antimicrobial peptide Protonectin (IL-12) into Nano micelle PEG-PCL on A549 adenocarcinoma lung cell line. J Polym Res 28, 341 (2021). https://doi.org/10.1007/s10965-021-02699-4

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