access icon free HER-2 aptamer-targeted Ecoflex® nanoparticles loaded with docetaxel promote breast cancer cells apoptosis and anti-metastatic effect

© The Institution of Engineering and Technology
Received 16/04/2018, Accepted 28/01/2019, Revised 21/11/2018, Published 06/02/2019

Breast cancer is a major cause of cancer mortality. Regarding the advantages of polymeric nanoparticles as drug delivery systems with targeting potential, in this study the antitumor mechanism of targeted docetaxel polymeric nanoparticles of Ecoflex® was exploited. Since the overexpression of HER-2 receptor in breast cancer cases is associated with poor prognosis and more aggressive disease, the proposed nanoparticles were conjugated to HER-2 specific aptamer molecules. In vitro cytotoxicity was evaluated by MTT assay. Flow-cytometry analysis was performed to evaluate the cellular uptake of nanoparticles loaded with a fluorescent probe. Anti-migration effects of samples were studied. Annexin IV-FITC and propidium iodide were implemented to investigate apoptosis induction and cell cycle analysis. Enhanced cytotoxicity compared with free docetaxel was explained considering improved cellular uptake of the nanoparticles and induced apoptosis in a larger portion of cells. Lower relative migration demonstrated enhanced anti-migration effect of nanoparticles, and cell cycle was arrested in G2/M phase using both formulations so the anti-microtubule mechanism of the drug was not altered. Therefore, this system could offer a potential substitute for the currently marketed docetaxel formulations, which may reduce adverse effects of the drug, while further in vivo and clinical investigations are required.

Inspec keywords: polymers; cell motility; drug delivery systems; nanoparticles; fluorescence; drugs; diseases; proteins; cancer; nanomedicine; biochemistry; toxicology; tumours; molecular biophysics; biomedical materials

Other keywords: HER-2 receptor; aggressive disease; fluorescent probe; antimetastatic effect; cell cycle; annexin IV-FITC; drug delivery systems; MTT assay; HER-2 specific aptamer molecules; cellular uptake; lower relative migration; breast cancer cell apoptosis; in vitro cytotoxicity; HER-2 aptamer-targeted Ecoflex nanoparticles; cancer mortality; apoptosis induction; antimicrotubule mechanism; flow-cytometry analysis; antitumor mechanism; propidium iodide; antimigration effect; targeted docetaxel polymeric nanoparticles

Subjects: Physical chemistry of biomolecular solutions and condensed states; Optical and laser radiation (medical uses); Patient care and treatment; Biological transport; cellular and subcellular transmembrane physics; Nanotechnology applications in biomedicine; Patient care and treatment; Biomedical materials

References

    1. 1)
      • 41. Ouyang, L., Li, L., Zhu, K., et al: ‘Docetaxel inhibits the migration and invasion of breast cancer cells by suppressing filopodia formation’, Tumor, 2013, 33, (9), pp. 776–780.
    2. 2)
      • 4. Lewis Phillips, G.D., Li, G., Dugger, D.L., et al: ‘Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate’, Cancer Res., 2008, 68, (22), pp. 9280–9290.
    3. 3)
      • 25. Chen, Z., Li, L., Zhao, H., et al: ‘Electrochemical impedance spectroscopy detection of lysozyme based on electrodeposited gold nanoparticles’, Talanta, 2011, 83, (5), pp. 1501–1506.
    4. 4)
      • 24. Chen, Z., Tai, Z., Gu, F., et al: ‘Aptamer-mediated delivery of docetaxel to prostate cancer through polymeric nanoparticles for enhancement of antitumor efficacy’, Eur. J. Pharm Biopharm., 2016, 107, pp. 130–141.
    5. 5)
      • 27. van Engeland, M., Nieland, L.J., Ramaekers, F.C., et al: ‘Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure’, Cytometry, 1998, 31, (1), pp. 1–9.
    6. 6)
      • 3. Rouzier, R., Perou, C.M., Symmans, W.F., et al: ‘Breast cancer molecular subtypes respond differently to preoperative chemotherapy’, Clin. Cancer Res., 2005, 11, pp. 5678–5685.
    7. 7)
      • 6. Chames, P., Van Regenmortel, M., Weiss, E., et al: ‘Therapeutic antibodies: successes, limitations and hopes for the future’, Br. J. Pharmacol., 2009, 157, (2), pp. 220–233.
    8. 8)
      • 40. Tran, T.H., Ramasamy, T., Choi, J.Y., et al: ‘Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells’, Int. J. Nanomed., 2015, 10, pp. 5249–5262.
    9. 9)
      • 16. Tabasi, A., Noorbakhsh, A., Sharifi, E.: ‘Reduced graphene oxide-chitosan-aptamer interface as new platform for ultrasensitive detection of human epidermal growth factor receptor 2’, BiosensBioelectron, 2017, 95, pp. 117–123.
    10. 10)
      • 1. Liu, F.C., Lin, H.T., Kuo, C.F., et al: ‘Epidemiology and survival outcome of breast cancer in a nationwide study’, Oncotarget, 2017, 8, (10), pp. 16939–16950.
    11. 11)
      • 34. Huynh, M.L., Fadok, V.A., Henson, P.M.: ‘Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation’, J. Clin. Invest, 2002, 109, (1), pp. 41–50.
    12. 12)
      • 29. EdalatFard, S., Tafvizi, F., BikhofTorbati, M.: ‘Silver nanoparticles biosynthesised usingCentellaasiatica leaf extract: apoptosisinduction in MCF-7 breast cancer cell line’, IET Nanobiotechnol.., 2018, 12, (7), pp. 994–1002.
    13. 13)
      • 26. Varshosaz, J., Riahi, S., Ghassami, E., et al: ‘Transferrin-targeted poly(butylene adipate) terephthalate nanoparticles for targeted delivery of 5-fluorouracil in HT29 colorectal cancer cell line’, J. BioactCompatPolym, 2017, 32, (5), pp. 503–527.
    14. 14)
      • 11. Baker, J., Ajani, J., Scotte, F., et al: ‘Docetaxel-related side effects and their management’, Eur. J. OncolNurs., 2008, 12, (3), pp. 253–268.
    15. 15)
      • 31. Majno, G., Joris, I.: ‘Apoptosis, oncosis, and necrosis. An overview of cell death’, Am. J. Pathol., 1995, 146, (1), pp. 3–15.
    16. 16)
      • 8. Peyrin, E.: ‘Nucleic acid aptamer molecular recognition principles and application in liquid chromatography and capillary electrophoresis’, J. Sep. Sci., 2009, 32, (10), pp. 1531–1536.
    17. 17)
      • 14. Varshosaz, J., Ghassami, E., Noorbakhsh, A., et al: ‘Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by electrospraying technique for docetaxel delivery in ovarian cancer induced mice’, Drug DevInd Pharm, 2018, 44, (6), pp. 1012–1022.
    18. 18)
      • 39. Luo, Y., Ling, Y., Guo, W., et al: ‘Docetaxel loaded oleic acid-coated hydroxyapatite nanoparticles enhance the docetaxel-induced apoptosis through activation of caspase-2 in androgen independent prostate cancer cells’, J. Control Release, 2010, 147, (2), pp. 278–288.
    19. 19)
      • 22. Xu, Z., Chen, L., Gu, W., et al: ‘The performance of docetaxel-loaded solid lipid nanoparticles targeted to hepatocellular carcinoma’, Biomaterials, 2009, 30, (2), pp. 226–232.
    20. 20)
      • 2. Bertucci, F., Finetti, P., Birnbaum, D.: ‘Basal breast cancer: a complex and deadly molecular subtype’. CurrMol Med., 2012, 12, (1), pp. 96–110.
    21. 21)
      • 37. Li, L., Tang, F., Liu, H., et al: ‘In vivo delivery of silica nanorattle encapsulated docetaxel for liver cancer therapy with low toxicity and high efficacy’, ACS Nano., 2010, 4, (11), pp. 6874–6882.
    22. 22)
      • 10. Haldar, S., Basu, A., Croce, C.M.: ‘Bcl-2 is The Guardian of microtubule integrity’, Cancer Res., 1997, 57, pp. 229–233.
    23. 23)
      • 33. Rock, K.L., Kono, H.: ‘The inflammatory response to cell death’, Annu Rev. Pathol., 2008, 3, pp. 99–126.
    24. 24)
      • 23. Le, X.F., Almeida, M.I., Mao, W., et al: ‘Modulation of MicroRNA-194 and cell migration by HER2-targeting trastuzumab in breast cancer’, Plos one, 2012, 7, (7), p. e41170.
    25. 25)
      • 13. Liua, Q., Li, R., Zhub, Z., et al: ‘Enhanced antitumor efficacy, biodistribution and penetration of docetaxel-loaded biodegradable nanoparticles’, Int. J. Pharm., 2012, 430, pp. 350–358.
    26. 26)
      • 9. Herbst, R.S., Khuri, F.R.: ‘Mode of action of docetaxel – a basis for combination with novel anticancer agents’, Cancer Treat Rev., 2003, 29, (5), pp. 407–415.
    27. 27)
      • 20. Varshosaz, J., Taymouri, S., Hassanzadeh, F., et al: ‘FolatedSynperonic-CholesterylHemisuccinate polymeric micelles for the targeted delivery of docetaxel in melanoma’, BioMed Res. Int., 2015, 2015, pp. 1–17.
    28. 28)
      • 18. Farokhzad, O.C., Jon, S., Khademhosseini, A., et al: ‘Nanoparticle-aptamerbioconjugates: a new approach for targeting prostate cancer cells’, Cancer, 2004, 64, (21), pp. 7668–7672.
    29. 29)
      • 15. Kim, M.Y., Jeong, S.: ‘In vitro selection of RNA aptamer and specific targeting of ErbB2 in breast cancer cells’, Nucleic. Acid. Ther., 2011, 21, pp. 73–178.
    30. 30)
      • 28. Pethig, R., Talary, M.S.: ‘Dielectrophoretic detection of membranemorphology changes in jurkat T-cells undergoingetoposide-induced apoptosis’, IET Nanobiotechnol.., 2007, 1, (1), pp. 2–9.
    31. 31)
      • 17. Ghassami, E., Varshosaz, J., Jahanian-najafabadi, A., et al: ‘Pharmacokinetics and in vitro/in vivo antitumor efficacy of aptamer-targeted ecoflex® nanoparticlesfor docetaxel delivery in ovarian cancer’, Int. J. Nanomed., 2018, 13, pp. 493–504.
    32. 32)
      • 5. Bauer, K.R., Brown, M., Cress, R.D., et al: ‘Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype’, Cancer, 2007, 109, (9), pp. 1721–1728.
    33. 33)
      • 35. Dorn, G.W.: ‘Molecular mechanisms that differentiate apoptosis from programmed necrosis’, Toxicologic Pathol., 2013, 41, pp. 227–234.
    34. 34)
      • 38. Liu, D., Wang, L., Zhihong Liu, Z., et al: ‘Preparation, characterization, and in vitro evaluation of docetaxel-loaded poly(lactic acid)-poly(ethylene glycol) nanoparticles for parenteral drug delivery’, J. Biomed. Nanotech., 2010, 6, pp. 675–682.
    35. 35)
      • 19. Farokhzad, O.C., Cheng, J., Teply, B.A., et al: ‘Targeted nanoparticle-aptamerbioconjugates for cancer chemotherapy in vivo’, Proc. Natl. Acad. Sci., 2006, 103, (16), pp. 6315–6320.
    36. 36)
      • 30. Kang, R., Zeh, H.J., Lotze, M.T., et al: ‘The beclin 1 network regulates autophagy and apoptosis’, Cell Death Differ., 2011, 18, (4), pp. 571–580.
    37. 37)
      • 21. Anido, J., Matar, P., Albanell, J., et al: ‘ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulinsignaling in her2-overexpressing breast cancer cells’, Clin. Cancer Res., 2003, 9, (4), pp. 1274–1283.
    38. 38)
      • 32. Manjo, G., La Gattuta, M., Thompson, T.E.: ‘Cellular death and necrosis: chemical, physical and morphologic changes in rat liver’, Virchows Arch PatholAnatPhysiolKlin Med, 1960, 333, pp. 421–465.
    39. 39)
      • 12. Esmaeli, B., Valero, V., Ahmadi, M.A., et al: ‘Canalicular stenosis secondary to docetaxel (Taxotere) a newly recognized side effect’, Am. Academy Ophthalmol., 2001, 108, (5), pp. 994–995.
    40. 40)
      • 7. O'Sullivan, C.K.: ‘Aptasensors – the future of biosensing’, Anal. BioanalChem., 2002, 372, (1), pp. 44–48.
    41. 41)
      • 36. Poon, I.K.H., Hulett, M.D., Parish, C.R.: ‘Molecular mechanisms of late apoptotic/necrotic cell clearance’, Cell Death Differ., 2010, 17, pp. 381–397.
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