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Peptide-conjugated micelles as a targeting nanocarrier for gene delivery

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Abstract

The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly(d,l-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells.

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References

  • Adiseshaiah PP, Hall JB, McNeil SE (2010) Nanomaterial standards for efficacy and toxicity assessment. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2:99–112

    Article  Google Scholar 

  • Alai M, Lin WJ (2014) Novel lansoprazole-loaded nanoparticles for the treatment of gastric acid secretion-related ulcers. In vitro and in vivo pharmacokinetic pharmacodynamic evaluation. AAPS J 16:361–372

    Article  Google Scholar 

  • Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5:505–515

    Article  Google Scholar 

  • Beletsi A, Panagi Z, Avgoustakis K (2005) Biodistribution properties of nanoparticles based on mixtures of PLGA with PLGA–PEG diblock copolymers. Int J Pharm 298:233–241

    Article  Google Scholar 

  • Betancourt T, Byrne JD, Sunaryo N, Crowder SW, Kadapakkam M, Patel S et al (2009) PEGylation strategies for active targeting of PLA/PLGA nanoparticles. J Biomed Mater Res 91A:263–276

    Article  Google Scholar 

  • Chittasupho C, Xie SX, Baoum A, Yakovleva T, Siahaan TJ, Berkland CJ (2009) ICAM-1 targeting of doxorubicin-loaded PLGA nanoparticles to lung epithelial cells. Eur J Pharm Sci 37:141–150

    Article  Google Scholar 

  • Choi SK, Verma M, Silpe J, Moody RE, Tang K, Hanson JJ et al (2012) A photochemical approach for controlled drug release in targeted drug delivery. Bioorg Med Chem 20:1281–1290

    Article  Google Scholar 

  • Couvreur P, Vauthier C (2006) Nanotechnology: intelligent design to treat complex disease. Pharm Res 23:1417–1450

    Article  Google Scholar 

  • Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Preat V (2012) PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 161:505–522

    Article  Google Scholar 

  • Eccles SA (2011) The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology. Int J Dev Biol 55:685–696

    Article  Google Scholar 

  • Hattori Y, Yamasaku H, Maitani Y (2013) Anionic polymer-coated lipoplex for safe gene delivery into tumor by systemic injection. J Drug Target 21:639–647

    Article  Google Scholar 

  • Jones CH, Chen CK, Ravikrishnan A, Rane S, Pfeifer BA (2013) Overcoming nonviral gene delivery barriers: perspective and future. Mol Pharm 10:4082–4098

    Article  Google Scholar 

  • Kamaly N, Xiao Z, Valencia PM, Radovic-Moreno AF, Farokhzad OC (2012) Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev 41:2971–3010

    Article  Google Scholar 

  • Li Z, Qiu L, Chen Q, Hao T, Qiao M, Zhao H et al (2015) pH-sensitive nanoparticles of poly(l-histidine)-poly(lactide-co-glycolide)-tocopheryl polyethylene glycol succinate for anti-tumor drug delivery. Acta Biomater 11:137–150

    Article  Google Scholar 

  • Lin WJ, Kao LT (2014) Cytotoxic enhancement of hexapeptide-conjugated micelles in epidermal growth factor receptor high-expressed cancer cells. Exp Opin Drug Del 11:1–14

    Google Scholar 

  • Liu CW, Lin WJ (2012) Polymeric nanoparticles conjugate a novel heptapeptide as an epidermal growth factor receptor-active targeting ligand for doxorubicin. Int J Nanomed 7:4749–4767

    Google Scholar 

  • Liu CW, Lin WJ (2013a) Using doxorubicin and siRNA loaded heptapeptide conjugated nanoparticles to enhance chemosensitization in epidermal growth factor receptor high-expressed breast cancer cells. J Drug Target 21:776–786

    Article  Google Scholar 

  • Liu CW, Lin WJ (2013b) Systemic co-delivery of doxorubicin and siRNA using nanoparticles conjugated with EGFR specific targeting peptide to enhance chemotherapy in ovarian tumor bearing mice. J Nano Res 15:1956–1969

    Article  Google Scholar 

  • Master A, Malamas A, Solanki R, Clausen DM, Eiseman JL, Sen Gupta A (2013) A cell-targeted photodynamic nanomedicine strategy for head and neck cancers. Mol Pharm 10:1988–1997

    Article  Google Scholar 

  • Mattson G, Conklin E, Desai S, Nielander G, Savage MD, Morgensen S (1993) A practical approach to crosslinking. Mol Biol Rep 17:167–183

    Article  Google Scholar 

  • Mickler FM, Mockl L, Ruthardt N, Ogris M, Wagner E, Brauchle C (2012) Tuning nanoparticle uptake: live-cell imaging reveals two distinct endocytosis mechanisms mediated by natural and artificial EGFR targeting ligand. Nano Lett 12:3417–3423

    Article  Google Scholar 

  • Milane L, Duan Z, Amij M (2011) Development of EGFR-targeted polymer blend nanocarriers for combination paclitaxel/lonidamine delivery to treat multi-drug resistance in human breast and ovarian tumor cells. Mol Pharm 8:185–203

    Article  Google Scholar 

  • Milella M, Nuzzo C, Bria E, Sperduti I, Buttitta F, Antoniani B et al (2012) EGFR molecular profiling in advanced NSCLC: a prospective phase II study in molecularly/clinically selected patients pretreated with chemotherapy. J Thorac Oncol 7:672–680

    Article  Google Scholar 

  • Oliveira MF, Guimaraes PP, Gomes AD, Suarez D, Sinisterra RD (2012) Strategies to target tumors using nanodelivery systems based on biodegradable polymers, aspects of intellectual property, and market. J Chem Biol 6:7–23

    Article  Google Scholar 

  • Pamujula S, Hazari S, Bolden G, Graves RA, Chinta DD, Dash S et al (2012) Cellular delivery of PEGylated PLGA nanoparticles. J Pharm Pharmacol 64:61–67

    Article  Google Scholar 

  • Ranganathan R, Madanmohan S, Kesavan A, Baskar G, Krishnamoorthy YR, Santosham R et al (2012) Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications. Int J Nanomedicine 7:1043–1060

    Google Scholar 

  • Rao NM, Gopal V (2006) Cell biological and biophysical aspects of lipid-mediated gene delivery. Biosci Rep 26:301–324

    Article  Google Scholar 

  • Reinehr R, Haussinger D (2012) CD95 death receptor and epidermal growth factor receptor (EGFR) in liver cell apoptosis and regeneration. Arch Biochem Biophys 518:2–7

    Article  Google Scholar 

  • Sakhrani NM, Padh H (2013) Organelle targeting: third level of drug targeting. Drug Des Dev Ther 7:585–599

    Google Scholar 

  • She ZG, Liu X, Kotamraju VR, Ruoslahti E (2014) Clot-targeted micellar formulation improves anticoagulation efficacy of bivalirudin. ACS Nano 8:10139–10149

    Article  Google Scholar 

  • Shroff K, Kokkoli E (2012) PEGylated liposomal doxorubicin targeted to alpha5beta1-expressing MDA-MB-231 breast cancer cells. Langmuir 28:4729–4736

    Article  Google Scholar 

  • Stella GM, Luisetti M, Inghilleri S, Cemmi F, Scabini R, Zorzetto M et al (2012) Targeting EGFR in non-small-cell lung cancer: lessons, experiences, strategies. Respir Med 106:173–183

    Article  Google Scholar 

  • Tada N, Horibe T, Haramoto M, Ohara K, Kohno M, Kawakami K (2011) A single replacement of histidine to arginine in EGFR-lytic hybrid peptide demonstrates the improved anticancer activity. Biochem Biophys Res Commun 407:383–388

    Article  Google Scholar 

  • Tahara K, Sakai T, Yamamoto H, Takeuchi H, Hirashima N, Kawashima Y (2011) Improvements in transfection efficiency with chitosan modified poly(dl-lactide-co-glycolide) nanospheres prepared by the emulsion solvent diffusion method for gene delivery. Chem Pharm Bull (Tokyo) 59:298–301

    Article  Google Scholar 

  • Tian HY, Tang ZH, Zhuang XL, Chen XS, Jing XB (2012) Biodegradable synthetic polymers: preparation, functionalization and biomedical application. Prog Polym Sci 37:237–280

    Article  Google Scholar 

  • Wang W, Li W, Ma N, Steinhoff G (2013) Non-viral gene delivery methods. Curr Pharm Biotechnol 14:46–60

    Google Scholar 

  • Xu J, Gattacceca F, Amiji M (2013) Biodistribution and pharmacokinetics of EGFR-targeted thiolated gelatin nanoparticles following systemic administration in pancreatic tumor-bearing mice. Mol Pharm 10:2031–2044

    Article  Google Scholar 

  • Yamamoto H, Tahara K, Kawashima Y (2012) Nanomedical system for nucleic acid drugs created with the biodegradable nanoparticle platform. J Microencapsul 29:54–62

    Article  Google Scholar 

  • Zajchowski DA, Karlan BY, Shawver LK (2012) Treatment-related protein biomarker expression differs between primary and recurrent ovarian carcinomas. Mol Cancer Ther 11:492–502

    Article  Google Scholar 

  • Zeng P, Xu Y, Zeng C, Ren H, Peng M (2011) Chitosan-modified poly(d,l-lactide-co-glycolide) nanospheres for plasmid DNA delivery and HBV gene-silencing. Int J Pharm 415:259–266

    Article  Google Scholar 

  • Zhang XX, Eden HS, Chen X (2012) Peptides in cancer nanomedicine: drug carriers, targeting ligands and protease substrates. J Control Release 159:2–13

    Article  Google Scholar 

  • Zhou W, Zhou Y, Wu J, Liu Z, Zhao H, Liu J, Ding J (2014) Aptamer-nanoparticle bioconjugates enhance intracellular delivery of vinorelbine to breast cancer cells. J Drug Target 22:57–66

    Article  Google Scholar 

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Acknowledgments

This work was supported by Ministry of Science and Technology in Taiwan (NSC 102-2320-B-002-007-MY3). The authors thank Dr. Fu Hsiung Chang for Zetasizer, Dr. Jin Long Chen for pEGFP-N1, Dr. Che-Ming Teng and Dr. I-Fen Chen for cell lines.

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Authors and Affiliations

  1. School of Pharmacy, Graduate Institute of Pharmaceutical Sciences, National Taiwan University, No. 33, Linsen S. Road, Taipei, 10050, Taiwan

    Wen Jen Lin & Wei Hsuan Chien

  2. Drug Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan

    Wen Jen Lin

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  1. Wen Jen Lin
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  2. Wei Hsuan Chien
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Correspondence to Wen Jen Lin.

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Lin, W.J., Chien, W.H. Peptide-conjugated micelles as a targeting nanocarrier for gene delivery. J Nanopart Res 17, 349 (2015). https://doi.org/10.1007/s11051-015-3132-0

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