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Evaluation of diverse peptidyl motifs for cellular delivery of semiconductor quantum dots

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Abstract

Cell-penetrating peptides (CPPs) have rapidly become a mainstay technology for facilitating the delivery of a wide variety of nanomaterials to cells and tissues. Currently, the library of CPPs to choose from is still limited, with the HIV TAT-derived motif still being the most used. Among the many materials routinely delivered by CPPs, nanoparticles are of particular interest for a plethora of labeling, imaging, sensing, diagnostic, and therapeutic applications. The development of nanoparticle-based technologies for many of these uses will require access to a much larger number of functional peptide motifs that can both facilitate cellular delivery of different types of nanoparticles to cells and be used interchangeably in the presence of other peptides and proteins on the same surface. Here, we evaluate the utility of four peptidyl motifs for their ability to facilitate delivery of luminescent semiconductor quantum dots (QDs) in a model cell culture system. We find that an LAH4 motif, derived from a membrane-inserting antimicrobial peptide, and a chimeric sequence that combines a sweet arrow peptide with a portion originating from the superoxide dismutase enzyme provide effective cellular delivery of QDs. Interestingly, a derivative of the latter sequence lacking just a methyl group was found to be quite inefficient, suggesting that even small changes can have significant functional outcomes. Delivery was effected using 1 h incubation with cells, and fluorescent counterstaining strongly suggests an endosomal uptake process that requires a critical minimum number or ratio of peptides to be displayed on the QD surface. Concomitant cytoviability testing showed that the QD–peptide conjugates are minimally cytotoxic in the model COS-1 cell line tested. Potential applications of these peptides in the context of cellular delivery of nanoparticles and a variety of other (bio)molecules are discussed.

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References

  1. Ho YP, Leong KW (2010) Nanoscale 2:60–68

    Article  CAS  Google Scholar 

  2. Janib SM, Moses AS, MacKay JA (2010) Adv Drug Deliv Rev 62:1052–1063

    Article  CAS  Google Scholar 

  3. Delehanty JB, Boeneman K, Bradburne CE, Robertson K, Medintz IL (2009) Expert Opin Drug Deliv 6:1091–1112

    Article  CAS  Google Scholar 

  4. Delehanty JB, Mattoussi H, Medintz IL (2009) Anal Bioanal Chem 393:1091–1105

    Article  CAS  Google Scholar 

  5. Algar WR, Prasuhn DE, Stewart MH, Jennings TL, Blanco-Canosa JB, Dawson PE, Medintz IL (2009) Bioconjugate Chem 22:825–858

    Article  Google Scholar 

  6. Sapsford KE, Algar WR, Berti L, Boeneman Gemmill K, Casey BJ, Oh E, Stewart MH, Medintz IL (2013) Chem Rev 113:1904–2074

    Article  CAS  Google Scholar 

  7. Duncan R, Richardson SC (2012) Mol Pharm 9:2380–2042

    Article  CAS  Google Scholar 

  8. Licht SS, Sonnleitner A, Weiss S, Schultz PG (2003) Biochemistry 42:2916–2925

    Article  CAS  Google Scholar 

  9. Delehanty JB, Bradburne CE, Boeneman K, Susumu K, Farrell D, Mei BC, Blanco-Canosa JB, Dawson G, Dawson PE, Mattoussi Medintz IL (2010) Integr Biol 2:265–277

    Article  CAS  Google Scholar 

  10. Algar WR, Susumu K, Delehanty JB, Medintz IL (2011) Anal Chem 83:8826–8837

    Article  CAS  Google Scholar 

  11. Walters R, Kraig RP, Medintz I, Delehanty JB, Stewart MH, Susumu K, Huston AL, Dawson PE, Dawson G (2012) ASN Neuro 4:e00099

    Article  Google Scholar 

  12. Boeneman Gemmill K, Delehanty JB, Blanco-Canosa JB, Susumu K, Stewart MH, Oh E, Huston AL, Dawson G, Ingale S, Walters R, Domowicz M, Deschamps JR, Algar WR, DiMaggio SC, Manono J, Spillmann CM, Thompson DA, Jennings TL, Dawson PE, Medintz IL (2013) ACS Nano (in press)

  13. Delehanty JB, Medintz IL, Pons T, Brunel FM, Dawson PE, Mattoussi H (2006) Bioconjugate Chem 17:920–927

    Article  CAS  Google Scholar 

  14. Blanco-Canosa JB, Medintz IL, Farrell D, Mattoussi H, Dawson PE (2010) J Am Chem Soc 132:10027–10033

    Article  CAS  Google Scholar 

  15. Sapsford KE, Farrell D, Sun S, Rasooly A, Mattoussi H, Medintz IL (2009) Sens Actuators B Chem 139:13–21

    Article  CAS  Google Scholar 

  16. Mei BC, Susumu K, Medintz IL, Delehanty JB, Mountziaris TJ, Mattoussi H (2008) J Mater Chem 18:4949–4958

    Article  CAS  Google Scholar 

  17. Mei BC, Susumu K, Medintz IL, Mattoussi H (2009) Nat Protoc 4:412–423

    Article  CAS  Google Scholar 

  18. Oh E, Delehanty JB, Sapsford KE, Susumu K, Goswami R, Blanco-Canosa JB, Dawson PE, Granek J, Shoff M, Zhang Q, Goering PL, Huston A, Medintz IL (2011) ACS Nano 5:6434–6448

    Article  CAS  Google Scholar 

  19. Sapsford KE, Pons T, Medintz IL, Higashiya S, Brunel FM, Dawson PE, Mattoussi H (2007) J Phys Chem C 111:11528–11538

    Article  CAS  Google Scholar 

  20. Dennis AM, Sotto D, Mei BC, Medintz IL, Mattoussi H, Bao G (2010) Bioconjugate Chem 21:1160–1170

    Article  CAS  Google Scholar 

  21. Liu W, Howarth M, Greytak AB, Zheng Y, Nocera DG, Ting AY, Bawendi MG (2008) J Am Chem Soc 130:1274–1284

    Article  CAS  Google Scholar 

  22. Boeneman K, Prasuhn DE, Blanco-Canosa JB, Dawson PE, Melinger JS, Ancona M, Stewart MH, Susumu K, Huston A, Medintz IL (2010) J Am Chem Soc 132:18177–18190

    Article  CAS  Google Scholar 

  23. Susumu K, Oh E, Delehanty JB, Blanco-Canosa JB, Johnson BJ, Jain V, Hervey WJ, Algar WR, Boeneman K, Dawson PE, Medintz IL (2011) J Am Chem Soc 133:9480–9496

    Article  CAS  Google Scholar 

  24. Boeneman Gemmill K, Deschamps JR, Delehanty JB, Susumu K, Stewart MH, Glaven RH, Anderson GP, Goldman ER, Huston AL, Medintz IL (2013) Bioconjugate Chem 24:269–281

    Article  CAS  Google Scholar 

  25. Boeneman K, Deschamps JR, Buckhout-White S, Prasuhn DE, Blanco-Canosa JB, Dawson PE, Stewart MH, Susumu K, Goldman ER, Ancona M, Medintz IL (2010) ACS Nano 4:7253–7266

    Article  CAS  Google Scholar 

  26. Sapsford KE, Granek J, Deschamps JR, Boeneman K, Blanco-Canosa JB, Dawson PE, Susumu K, Stewart MH, Medintz IL (2011) ACS Nano 5:2687–2699

    Article  CAS  Google Scholar 

  27. Lo SL, Wang S (2008) Biomaterials 29:2408e14

    Article  Google Scholar 

  28. Midoux P, Monsigny M (1999) Bioconjugate Chem 10:406–411

    Article  CAS  Google Scholar 

  29. Midoux P, Pichon C, Yaounac JJ, Jaffrès (2009) Br J Pharmacol 157:166-178

  30. Leng Q, Scaria P, Zhu J, Ambulos N, Campbell P, Mixson AJ (2005) J Gene Med 7:977–986

    Article  CAS  Google Scholar 

  31. Vogt TC, Bechinger B (1999) J Biol Chem 274:29115–29121

    Article  CAS  Google Scholar 

  32. Mason AJ, Gasnier C, Bechinger B (2006) Antimicrob. Agents Chemother 50:3305–3311

    Google Scholar 

  33. Bechinger B (1996) J Mol Biol 263:768–775

    Article  CAS  Google Scholar 

  34. De Coupade C, Fittipaldi A, Chagnas V, Michel M, Carlier S, Tasciotti E, Darmon A, Ravel D, Kearsey J, Giacca M, Cailler F (2005) Biochem J 390:407–418

    Article  Google Scholar 

  35. Crespo L, Sanclimens G, Montaner B, Perez-Tomas R, Royo M, Pons M, Albericio F, Giralt E (2002) J Am Chem Soc 124:8876–8883

    Article  CAS  Google Scholar 

  36. Fernandez-Carneado J, Kogan MJ, Castel S, Giralt E (2004) Angew Chem Int Ed 43:1811–1814

    Article  CAS  Google Scholar 

  37. Fernandez-Carneado J, Kogan MJ, Pujals S, Giralt E (2004) Biopolymers 76:196–203

    Article  CAS  Google Scholar 

  38. Delehanty JB, Boeneman K, Bradburne CE, Robertson K, Bongard JE, Medintz IL (2010) Ther Deliv 1:411–433

    Article  CAS  Google Scholar 

  39. Prasuhn DE, Deschamps JR, Susumu K, Stewart MH, Boeneman K, Blanco-Canosa JB, Dawson PE, Medintz IL (2010) Small 6:555–564

    Article  CAS  Google Scholar 

  40. Medintz IL, Pons T, Delehanty JB, Susumu K, Brunel FM, Dawson PE, Mattoussi H (2008) Bioconjugate Chem 19:1785–1795

    Article  CAS  Google Scholar 

  41. Cheng Y, Zak O, Aisen P, Harrison SC, Walz T (2004) Cell 116:565-576

    Google Scholar 

Download references

Acknowledgments

The authors acknowledge NRL NSI and DTRA JSTO MIPR # B112582M for financial support. M.M. acknowledges funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement number 254897.

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Authors and Affiliations

  1. Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC, 20375, USA

    Kelly Boeneman Gemmill, James B. Delehanty & Igor L. Medintz

  2. Division of Optical Sciences Code 5600, U.S. Naval Research Laboratory, Washington, DC, 20375, USA

    Michael H. Stewart & Kimihiro Susumu

  3. Departments of Chemistry and Cell Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA

    Markus Muttenthaler & Philip E. Dawson

  4. Sotera Defense Solutions, Annapolis Junction, MD, 20701, USA

    Kimihiro Susumu

Authors
  1. Kelly Boeneman Gemmill
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  2. Markus Muttenthaler
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  3. James B. Delehanty
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  4. Michael H. Stewart
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  5. Kimihiro Susumu
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  6. Philip E. Dawson
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  7. Igor L. Medintz
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Corresponding author

Correspondence to Igor L. Medintz.

Additional information

Published in the topical collection Optical Nanosensing in Cells with guest editor Francesco Baldini.

Kelly Boeneman Gemmill and Markus Muttenthaler contributed equally to this contribution.

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Gemmill, K.B., Muttenthaler, M., Delehanty, J.B. et al. Evaluation of diverse peptidyl motifs for cellular delivery of semiconductor quantum dots. Anal Bioanal Chem 405, 6145–6154 (2013). https://doi.org/10.1007/s00216-013-6982-2

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  • DOI: https://doi.org/10.1007/s00216-013-6982-2

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