A single-layer peptide nanofiber for enhancing the cytotoxicity of trastuzumab (anti-HER)
Source abstract
Abstract
A multivalent system is often employed to enhance the effectiveness of a targeted therapy. In the present study, we report a single-layer peptide nanofiber (NFP) as a multivalent targeting platform to improve the cytotoxicity of trastuzumab (anti-HER), a monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER-2) in approximately 20 % of breast cancer patients. The trastuzumab-conjugated nanofiber (anti-HER/NFP) was 100 × 4 nm in size and was assembled from multiple peptide units (mPEG-BK(FITC)SGASNRA-kldlkldlkldl-CONH2). The optimized preparation was attached with approximately 10 antibodies at the surface. Because of an increase in the multivalency, anti-HER/NFP was able to truncate more cell surface HER-2 and, thus, showed an enhanced cytotoxicity toward HER-2 positive SKBr-3 human breast cancer as compared to the free anti-HER. Western blot analysis and fluorescence microscopic studies confirmed that there was a significant downregulation of the HER-2 level and also inhibition of the cell survival cell signaling pathways including the phosphatidylinositol 3-kinase (PI3K) and the mitogen activated protein kinase (MAPK) pathway. Our data suggested that NFP can be useful as a multivalent platform for immunotherapy, especially in combination with other chemotherapeutic agents in the future.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Monoclonal and Polyclonal Antibodies Research · HER2/EGFR in Cancer Research · Peptidase Inhibition and Analysis
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (66)
Show source-provided references
1. Abraham R, Moller D, Gabel D, Senter P, Hellström I, Hellström KE (1991) The influence of periodate oxidation on monoclonal antibody avidity and immunoreactivity. J Immunol Methods 144(1):77–86. doi: 10.1016/0022-1759(91)90233-610.1016/0022-1759(91)90233-6 ↗
2. Albrecht H, Denardo GL, Denardo SJ (2006) Monospecific bivalent scFv-SH: effects of linker length and location of an engineered cysteine on production, antigen binding activity and free SH accessibility. J Immunol Methods 310(1–2):100–116. doi: 10.1016/j.jim.2005.12.01210.1016/j.jim.2005.12.012 ↗
3. Barat B, Sirk SJ, McCabe KE, Li J, Lepin EJ, Remenyi R, Koh AL, Olafsen T, Gambhir SS, Weiss S, Wu AM (2009) Cys-diabody quantum dot conjugates (immunoQdots) for cancer marker detection. Bioconjug Chem 20(8):1474–1481. doi: 10.1021/bc800421f10.1021/bc800421f ↗
4. Ben-Kasus T, Schechter B, Sela M, Yarden Y (2007) Cancer therapeutic antibodies come of age: targeting minimal residual disease. Mol Oncol 1(1):42–54. doi: 10.1016/j.molonc.2007.01.00310.1016/j.molonc.2007.01.003 ↗
5. Ben-Kasus T, Schechter B, Lavi S, Yarden Y, Sela M (2009) Persistent elimination of ErbB-2/HER2-overexpressing tumors using combinations of monoclonal antibodies: relevance of receptor endocytosis. Proc Natl Acad Sci USA 106(9):3294–3299. doi: 10.1073/pnas.081205910610.1073/pnas.0812059106 ↗
6. Carter PJ (2006) Potent antibody therapeutics by design. Nat Rev Immunol 6(5):343–357. doi: 10.1038/nri183710.1038/nri1837 ↗
7. Chan AC, Carter PJ (2010) Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol 10(5):301–316. doi: 10.1038/nri276110.1038/nri2761 ↗
8. Chiu GN, Edwards LA, Kapanen AI, Malinen MM, Dragowska WH, Warburton C, Chikh GG, Fang KY, Tan S, Sy J, Tucker C, Waterhouse DN, Klasa R, Bally MB (2007) Modulation of cancer cell survival pathways using multivalent liposomal therapeutic antibody constructs. Mol Cancer Ther 6(3):844–855. doi: 10.1158/1535-7163.MCT-06-015910.1158/1535-7163.MCT-06-0159 ↗
9. Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ (1999) Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 17(9):263910.1200/JCO.1999.17.9.2639 ↗
10. Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH (2010) Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 28(1):92–98. doi: 10.1200/JCO.2008.19.984410.1200/JCO.2008.19.9844 ↗
11. De Santes K, Slamon D, Anderson SK, Shepard M, Fendly B, Maneval D, Press O (1992) Radiolabeled antibody targeting of the HER-2/neu oncoprotein. Cancer Res 52(7):1916–1923
12. Dirix LY, Rutten A, Huget P, Dirix M (2013) Trastuzumab emtansine in breast cancer. Expert Opin Biol Ther 13(4):607–614. doi: 10.1517/14712598.2013.77823810.1517/14712598.2013.778238 ↗
13. Ewer SM, Ewer MS (2008) Cardiotoxicity profile of trastuzumab. Drug Saf 31(6):459–46710.2165/00002018-200831060-00002 ↗
14. Gao H, Shi W, Freund LB (2005) Mechanics of receptor-mediated endocytosis. Proc Natl Acad Sci USA 102(27):9469–9474. doi: 10.1073/pnas.050387910210.1073/pnas.0503879102 ↗
15. Gelain F, Bottai D, Vescovi A, Zhang S (2006) Designer self-assembling peptide nanofiber scaffolds for adult mouse neural stem cell 3-dimensional cultures. PLoS One 1:e119. doi: 10.1371/journal.pone.000011910.1371/journal.pone.0000119 ↗
16. Ghosh R, Narasanna A, Wang SE, Liu S, Chakrabarty A, Balko JM, Gonzalez-Angulo AM, Mills GB, Penuel E, Winslow J, Sperinde J, Dua R, Pidaparthi S, Mukherjee A, Leitzel K, Kostler WJ, Lipton A, Bates M, Arteaga CL (2011) Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers. Cancer Res 71(5):1871–1882. doi: 10.1158/0008-5472.CAN-10-187210.1158/0008-5472.CAN-10-1872 ↗
17. Gratton SE, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ, Napier ME, DeSimone JM (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA 105(33):11613–11618. doi: 10.1073/pnas.080176310510.1073/pnas.0801763105 ↗
18. Haun JB, Devaraj NK, Hilderbrand SA, Lee H, Weissleder R (2010) Bioorthogonal chemistry amplifies nanoparticle binding and enhances the sensitivity of cell detection. Nat Nanotechnol 5(9):660–665. doi: 10.1038/nnano.2010.14810.1038/nnano.2010.148 ↗
19. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4(12):988–1004. doi: 10.1038/nrd190210.1038/nrd1902 ↗
20. Honegger A (2008) Engineering antibodies for stability and efficient folding. Handb Exp Pharmacol 181:47–68. doi: 10.1007/978-3-540-73259-4_310.1007/978-3-540-73259-4_3 ↗
21. Hu K, Li J, Shen Y, Lu W, Gao X, Zhang Q, Jiang X (2009) Lactoferrin-conjugated PEG-PLA nanoparticles with improved brain delivery: in vitro and in vivo evaluations. J Control Release 134(1):55–61. doi: 10.1016/j.jconrel.2008.10.01610.1016/j.jconrel.2008.10.016 ↗
22. Husain M, Bieniarz C (1994) Fc of site-specific labeling immunoglobulins with calf intestinal alkaline phosphatase. Bioconjug Chem 5(5):482–490. doi: 10.1021/bc00029a01710.1021/bc00029a017 ↗
23. Jiang W, Kim BY, Rutka JT, Chan WC (2008) Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol 3(3):145–150. doi: 10.1038/nnano.2008.3010.1038/nnano.2008.30 ↗
24. Junttila TT, Parsons K, Olsson C, Lu Y, Xin Y, Theriault J, Crocker L, Pabonan O, Baginski T, Meng G, Totpal K, Kelley RF, Sliwkowski MX (2010) Superior in vivo efficacy of afucosylated trastuzumab in the treatment of HER2-amplified breast cancer. Cancer Res 70(11):4481–4489. doi: 10.1158/0008-5472.CAN-09-370410.1158/0008-5472.CAN-09-3704 ↗
25. Kandzari DE, Hasselblad V, Tcheng JE, Stone GW, Califf RM, Kastrati A, Neumann FJ, Brener SJ, Montalescot G, Kong DF, Harrington RA (2004) Improved clinical outcomes with abciximab therapy in acute myocardial infarction: a systematic overview of randomized clinical trials. Am Heart J 147(3):457–462. doi: 10.1016/j.ahj.2003.08.01110.1016/j.ahj.2003.08.011 ↗
26. Kaufman B, Mackey JR, Clemens MR, Bapsy PP, Vaid A, Wardley A, Tjulandin S, Jahn M, Lehle M, Feyereislova A, Revil C, Jones A (2009) Trastuzumab plus anastrozole versus anastrozole alone for the treatment of postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer: results from the randomized phase III TAnDEM study. J Clin Oncol 27(33):5529–5537. doi: 10.1200/JCO.2008.20.684710.1200/JCO.2008.20.6847 ↗
27. Khan JA, Kudgus RA, Szabolcs A, Dutta S, Wang E, Cao S, Curran GL, Shah V, Curley S, Mukhopadhyay D, Robertson JD, Bhattacharya R, Mukherjee P (2011) Designing nanoconjugates to effectively target pancreatic cancer cells in vitro and in vivo. PLoS One 6(6):e20347. doi: 10.1371/journal.pone.002034710.1371/journal.pone.0020347 ↗
28. Koutsopoulos S, Unsworth LD, Nagai Y, Zhang S (2009) Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold. Proc Natl Acad Sci USA 106(12):4623–4628. doi: 10.1073/pnas.080750610610.1073/pnas.0807506106 ↗
29. Kubetzko S, Balic E, Waibel R, Zangemeister-Wittke U, Pluckthun A (2006) PEGylation and multimerization of the anti-p185HER-2 single chain Fv fragment 4D5: effects on tumor targeting. J Biol Chem 281(46):35186–35201. doi: 10.1074/jbc.M60412720010.1074/jbc.M604127200 ↗
30. Kumar R, Shepard HM, Mendelsohn J (1991) Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. Mol Cell Biol 11(2):979–98610.1128/MCB.11.2.979 ↗
31. Law B, Tung CH (2008) Structural modification of protease inducible preprogrammed nanofiber precursor. Biomacromolecules 9(2):421–425. doi: 10.1021/bm701202610.1021/bm7012026 ↗
32. Law B, Weissleder R, Tung CH (2007) Protease-sensitive fluorescent nanofibers. Bioconjug Chem 18(6):1701–1704. doi: 10.1021/bc070054z10.1021/bc070054z ↗
33. Liu HY, Gao X (2011) Engineering monovalent quantum dot-antibody bioconjugates with a hybrid gel system. Bioconjug Chem 22(3):510–517. doi: 10.1021/bc200004z10.1021/bc200004z ↗
34. Malik R, Qian S, Law B (2011) Design and synthesis of a near-infrared fluorescent nanofiber precursor for detecting cell-secreted urokinase activity. Anal Biochem 412(1):26–33. doi: 10.1016/j.ab.2011.01.01010.1016/j.ab.2011.01.010 ↗
35. Matson JB, Stupp SI (2011) Drug release from hydrazone-containing peptide amphiphiles. Chem Commun (Camb) 47(28):7962–7964. doi: 10.1039/c1cc12570b10.1039/c1cc12570b ↗
36. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357(26):2666–2676. doi: 10.1056/NEJMoa07211310.1056/NEJMoa072113 ↗
37. Misinzo G, Delputte PL, Nauwynck HJ (2008) Inhibition of endosome-lysosome system acidification enhances porcine circovirus 2 infection of porcine epithelial cells. J Virol 82(3):1128–1135. doi: 10.1128/JVI.01229-0710.1128/JVI.01229-07 ↗
38. Muro S, Cui X, Gajewski C, Murciano JC, Muzykantov VR, Koval M (2003) Slow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress. Am J Physiol Cell Physiol 285(5):C1339–C1347. doi: 10.1152/ajpcell.00099.200310.1152/ajpcell.00099.2003 ↗
39. Muro S, Dziubla T, Qiu W, Leferovich J, Cui X, Berk E, Muzykantov VR (2006) Endothelial targeting of high-affinity multivalent polymer nanocarriers directed to intercellular adhesion molecule 1. J Pharmacol Exp Ther 317(3):1161–1169. doi: 10.1124/jpet.105.09897010.1124/jpet.105.098970 ↗
40. Pai JC, Sutherland JN, Maynard JA (2009) Progress towards recombinant anti-infective antibodies. Recent Pat Antiinfect Drug Discov 4(1):1–17. doi: 10.2174/157489109787236319
41. Park BH, Davidson NE (2007) PI3 kinase activation and response to Trastuzumab Therapy: what’s neu with herceptin resistance? Cancer Cell 12(4):297–299. doi: 10.1016/j.ccr.2007.10.00410.1016/j.ccr.2007.10.004 ↗
42. Perego D, Masciocchi N, Guagliardi A, Manuel Dominguez-Vera J, Galvez N (2013) Poly(amino acid) functionalized maghemite and gold nanoparticles. Nanotechnology 24(7):075102. doi: 10.1088/0957-4484/24/7/07510210.1088/0957-4484/24/7/075102 ↗
43. Pohlmann PR, Mayer IA, Mernaugh R (2009) Resistance to Trastuzumab in Breast Cancer. Clin Cancer Res 15(24):7479–7491. doi: 10.1158/1078-0432.CCR-09-063610.1158/1078-0432.CCR-09-0636 ↗
44. Pouniotis DS, Apostolopoulos V, Pietersz GA (2006) Penetratin tandemly linked to a CTL peptide induces anti-tumour T-cell responses via a cross-presentation pathway. Immunology 117(3):329–339. doi: 10.1111/j.1365-2567.2005.02304.x10.1111/j.1365-2567.2005.02304.x ↗
45. Rajangam K, Behanna HA, Hui MJ, Han X, Hulvat JF, Lomasney JW, Stupp SI (2006) Heparin binding nanostructures to promote growth of blood vessels. Nano Lett 6(9):2086–2090. doi: 10.1021/nl061355510.1021/nl0613555 ↗
46. Rayson D, Richel D, Chia S, Jackisch C, van der Vegt S, Suter T (2008) Anthracycline-trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies. Ann Oncol 19(9):1530–1539. doi: 10.1093/annonc/mdn29210.1093/annonc/mdn292 ↗
47. Reichert JM, Rosensweig CJ, Faden LB, Dewitz MC (2005) Monoclonal antibody successes in the clinic. Nat Biotechnol 23(9):1073–1078. doi: 10.1038/nbt0905-107310.1038/nbt0905-1073 ↗
48. Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN (2009) The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 14(4):320–368. doi: 10.1634/theoncologist.2008-023010.1634/theoncologist.2008-0230 ↗
49. Safenkova IV, Zherdev AV, Dzantiev BB (2010) Correlation between the composition of multivalent antibody conjugates with colloidal gold nanoparticles and their affinity. J Immunol Methods 357(1–2):17–25. doi: 10.1016/j.jim.2010.03.01010.1016/j.jim.2010.03.010 ↗
50. Schoonooghe S, Kaigorodov V, Zawisza M, Dumolyn C, Haustraete J, Grooten J, Mertens N (2009) Efficient production of human bivalent and trivalent anti-MUC1 Fab-scFv antibodies in Pichia pastoris. BMC Biotechnol 9:70. doi: 10.1186/1472-6750-9-7010.1186/1472-6750-9-70 ↗
51. Shahied LS, Tang Y, Alpaugh RK, Somer R, Greenspon D, Weiner LM (2004) Bispecific minibodies targeting HER2/neu and CD16 exhibit improved tumor lysis when placed in a divalent tumor antigen binding format. J Biol Chem 279(52):53907–53914. doi: 10.1074/jbc.M40788820010.1074/jbc.M407888200 ↗
52. Shukla R, Thomas TP, Peters JL, Desai AM, Kukowska-Latallo J, Patri AK, Kotlyar A, Baker JR Jr (2006) HER2 specific tumor targeting with dendrimer conjugated anti-HER2 mAb. Bioconjug Chem 17(5):1109–1115. doi: 10.1021/bc050348p10.1021/bc050348p ↗
53. Shuvaev VV, Ilies MA, Simone E, Zaitsev S, Kim Y, Cai S, Mahmud A, Dziubla T, Muro S, Discher DE, Muzykantov VR (2011) Endothelial targeting of antibody-decorated polymeric filomicelles. ACS Nano 5(9):6991–6999. doi: 10.1021/nn201545310.1021/nn2015453 ↗
54. Snyder SL, Sobocinski PZ (1975) An improved 2,4,6-trinitrobenzenesulfonic acid method for the determination of amines. Anal Biochem 64(1):284–288. doi: 10.1016/0003-2697(75)90431-510.1016/0003-2697(75)90431-5 ↗
55. Spector NL, Blackwell KL (2009) Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 27(34):5838–5847. doi: 10.1200/JCO.2009.22.150710.1200/JCO.2009.22.1507 ↗
56. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3):719–72610.1200/JCO.20.3.719 ↗
57. Wagh A, Singh J, Qian S, Law B (2012) A short circulating peptide nanofiber as a carrier for tumoral delivery. Nanomedicine. doi: 10.1016/j.nano.2012.10.009
58. Wang J, Tian S, Petros RA, Napier ME, Desimone JM (2010) The complex role of multivalency in nanoparticles targeting the transferrin receptor for cancer therapies. J Am Chem Soc 132(32):11306–11313. doi: 10.1021/ja104317710.1021/ja1043177 ↗
59. Wangler C, Moldenhauer G, Eisenhut M, Haberkorn U, Mier W (2008) Antibody-dendrimer conjugates: the number, not the size of the dendrimers, determines the immunoreactivity. Bioconjug Chem 19(4):813–820. doi: 10.1021/bc700308q10.1021/bc700308q ↗
60. Webber MJ, Tongers J, Newcomb CJ, Marquardt KT, Bauersachs J, Losordo DW, Stupp SI (2011) Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair. Proc Natl Acad Sci USA 108(33):13438–13443. doi: 10.1073/pnas.101654610810.1073/pnas.1016546108 ↗
61. Wiechelman KJ, Braun RD, Fitzpatrick JD (1988) Investigation of the bicinchoninic acid protein assay: identification of the groups responsible for color formation. Anal Biochem 175(1):231–23710.1016/0003-2697(88)90383-1 ↗
62. Wiltzius JJ, Landau M, Nelson R, Sawaya MR, Apostol MI, Goldschmidt L, Soriaga AB, Cascio D, Rajashankar K, Eisenberg D (2009) Molecular mechanisms for protein-encoded inheritance. Nat Struct Mol Biol 16(9):973–978. doi: 10.1038/nsmb.164310.1038/nsmb.1643 ↗
63. Yu YX, Shen L, Xia P, Tang YW, Bao L, Pei G (2006) Syntaxin 1A promotes the endocytic sorting of EAAC1 leading to inhibition of glutamate transport. J Cell Sci 119(Pt 18):3776–3787. doi: 10.1242/jcs.0315110.1242/jcs.03151 ↗
64. Yuan Q, Cai S, Zhang X, Liu Z, Li Z, Luo X, Xiong C, Wang J, Hu J, Ruan J (2012) A new protoapigenone analog RY10-4 induces apoptosis and suppresses invasion through the PI3K/Akt pathway in human breast cancer. Cancer Lett 324(2):210–220. doi: 10.1016/j.canlet.2012.05.02510.1016/j.canlet.2012.05.025 ↗
65. Zhang S, Gelain F, Zhao X (2005) Designer self-assembling peptide nanofiber scaffolds for 3D tissue cell cultures. Semin Cancer Biol 15(5):413–420. doi: 10.1016/j.semcancer.2005.05.00710.1016/j.semcancer.2005.05.007 ↗
66. Zhao F, Zhao Y, Liu Y, Chang X, Chen C (2011) Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 7(10):1322–1337. doi: 10.1002/smll.20110000110.1002/smll.201100001 ↗