Skip to main content
SpringerLink
Log in

Clinical translational challenges in nanomedicine

  • Organic Nanoparticles for Drug Delivery and Imaging
  • Published:
MRS Bulletin Aims and scope Submit manuscript

Abstract

After a decade of active research, pressure is mounting for clinical translation of nanomedicines. However, to enable success in the clinic, it is important to understand the factors that can pose challenges. For example, reduction in adverse effects alone might not be enough of a driver today for clinical translation. The benchmark for clinical translation will be increased efficacy, a significant challenge to overcome if nanomedicines are developed only from a drug delivery perspective. Success in clinics will therefore require a re-examination of the design of nanomedicines, including challenging current dogmas. What can we learn from translational experience with recently approved antibody-drug conjugates, which like nanomedicines is another approach to deliver chemotherapy agents selectively to the tumors? Nanomedicines can address some of the emerging challenges in cancer chemotherapy, including heterogeneity and adaptive resistance, which can offer unique translational opportunities. This article addresses some of these themes and strategies that can facilitate translation of nanomedicines to the clinic.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2

Similar content being viewed by others

References

  1. M. Ferrari, Nat. Rev. Cancer 5, 161 (2005).

    Google Scholar 

  2. A.Z. Wang, R. Langer, O.C. Farokhzad, Annu. Rev. Med. 63, 185 (2012).

    Google Scholar 

  3. S.M. Moghimi, A.C. Hunter, J.C. Murray. Pharmacol. Rev. 53, 283 (2001).

  4. J.M. Marjan, T.M. Allen, Biotechnol. Adv. 14, 151 (1996).

    Google Scholar 

  5. T.M. Allen, P.R. Cullis, Adv. Drug Deliv. Rev. 65, 36 (2013).

    Google Scholar 

  6. F. Yuan, M. Dellian, D. Fukumura, M. Leunig, D.A. Berk, V.P. Torchilin, R.K. Jain, Cancer Res. 55, 3752 (1995).

    Google Scholar 

  7. F. Yuan, M. Leunig, S.K. Huang, D.A. Berk, D. Papahadjopoulos, R.K. Jain, Cancer Res. 54, 3352 (1994).

    Google Scholar 

  8. D.W. Northfelt, F.J. Martin, P. Working, P.A. Volberding, J. Russell, M Newman, M.A. Amantea, L.D. Kaplan, J. Clin. Pharmacol. 36, 55 (1996).

    Google Scholar 

  9. Y. Barenholz, J. Control. Release 160, 117 (2012).

    Google Scholar 

  10. G. Batist, J. Barton, P. Chaikin, C. Swenson, L. Welles, Expert Opin. Pharmacother. 3, 1739 (2002).

    Google Scholar 

  11. N. Desai, V. Trieu, Z. Yao, L. Louie, S. Ci, A. Yang, C. Tao, T. De, B. Beals, D. Dykes, P. Noker, R. Yao, E. Labao, M. Hawkins, P. Soon-Shiong, Clin. Cancer Res. 12, 1317 (2006).

    Google Scholar 

  12. Y. Malam, M. Loizidou, A.M. Seifalian, Trends Pharmacol. Sci. 30, 592 (2009).

    Google Scholar 

  13. P. Ma, R.J. Mumper, J. Nanomed. Nanotechnol. 4, 1000164 (2013).

    Google Scholar 

  14. F. Alexis, E. Pridgen, L.K. Molnar, O.C. Farokhzad, Mol. Pharm. 5, 505 (2008).

    Google Scholar 

  15. G. Song, H. Wu, K. Yoshino, W.C. Zamboni, J. Liposome Res. 22, 177 (2012).

    Google Scholar 

  16. R. Gref, M. Lück, P. Quellec, M. Marchand, E. Dellacherie, S. Harnisch, T. Blunk, R.H. Müller, Colloids Surf. B, Biointerfaces 18, 301 (2000).

    Google Scholar 

  17. J.F. Stefanick, J.D. Ashley, T. Kiziltepe, B. Bilgicer, ACS Nano 7, 2935 (2013).

    Google Scholar 

  18. S.D. Li, L. Huang, J. Control. Release 145, 178 (2010).

    Google Scholar 

  19. A. Albanese, P.S. Tang, W.C. Chan, Annu. Rev. Biomed. Eng. 14, 1 (2012).

    Google Scholar 

  20. S.M. Loverde, M.L. Klein, D.E. Discher, Adv. Mater. 24, 3823 (2012).

    Google Scholar 

  21. B.D. Chithrani, W.C. Chan, Nano Lett. 7, 1542 (2007).

    Google Scholar 

  22. H.S. Choi, W. Liu, P. Misra, E. Tanaka, J.P. Zimmer, B. Itty Ipe, M.G. Bawendi, J.V. Frangioni, Nat. Biotechnol. 25, 1165 (2007).

    Google Scholar 

  23. R.K. Jain, T. Stylianopoulos, Nat. Rev. Clin. Oncol. 7, 653 (2010).

    Google Scholar 

  24. V.P. Chauhan, T. Stylianopoulos, J.D. Martin, Z. Popović, O. Chen, W.S. Kamoun, M.G. Bawendi, D. Fukumura, R.K. Jain, Nat. Nanotechnol. 7, 383 (2012).

    Google Scholar 

  25. M.E. O’Brien, N. Wigler, M. Inbar, R. Rosso, E. Grischke, A. Santoro, R. Catane, D.G. Kieback, P. Tomczak, S.P. Ackland, F. Orlandi, L. Mellars, L. Alland, C. Tendler, CAELYX Breast Cancer Study Group, Ann. Oncol. 15, 440 (2004).

    Google Scholar 

  26. S. Chan, N. Davidson, E. Juozaityte, F. Erdkamp, A. Pluzanska, N. Azarnia, L.W. Lee, Ann. Oncol. 15, 1527 (2004).

    Google Scholar 

  27. P. Chaudhuri, R. Harfouche, S. Soni, D.M. Hentschel, S. Sengupta, ACS Nano 4, 574 (2010).

    Google Scholar 

  28. P. Chaudhuri, A. Paraskar, S. Soni, R.A. Mashelkar, S. Sengupta, ACS Nano 3, 2505 (2009).

    Google Scholar 

  29. P. Chaudhuri, S. Soni, S. Sengupta, Nanotechnology 21, 025102 (2010).

    Google Scholar 

  30. L. Kelland, Nat. Rev. Cancer 7, 573 (2007).

    Google Scholar 

  31. N.E. Madias, J.T. Harrington, Am. J. Med. 65, 307 (1978).

    Google Scholar 

  32. T. Al-Khatib, N. Cohen, A.S. Carret, S. Daniel, Int. J. Pediatr. Otorhinolaryngol. 74, 913 (2010).

    Google Scholar 

  33. S.C. White, P. Lorigan, G.P. Margison, J.M. Margison, F. Martin, N. Thatcher, H. Anderson, M. Ranson, Br. J. Cancer 95, 822 (2006).

    Google Scholar 

  34. W.C. Zamboni, A.C. Gervais, M.J. Egorin, J.H. Schellens, E.G. Zuhowski, D. Pluim, E. Joseph, D.R. Hamburger, P.K. Working, G. Colbern, M.E. Tonda, D.M. Potter, J.L. Eiseman, Cancer Chemother. Pharmacol. 53, 329 (2004).

    Google Scholar 

  35. K. Avgoustakis, A. Beletsi, Z. Panagi, P. Klepetsanis, A.G. Karydas, D.S. Ithakissios, J. Control. Release 79, 123 (2002).

    Google Scholar 

  36. J. Fujiyama, Y. Nakase, K. Osaki, C. Sakakura, H. Yamagishi, A. Hagiwara, J. Control. Release 89, 397 (2003).

    Google Scholar 

  37. S. Dhar, F.X. Gu, R. Langer, O.C. Farokhzad, S.J. Lippard, Proc. Natl. Acad. Sci. U.S.A. 105, 17356 (2008).

    Google Scholar 

  38. K.J. Haxton, M.H. Burt, J. Pharm. Sci. 98, 2299 (2009).

    Google Scholar 

  39. J.M. Rademaker-Lakhai, C. Terret, S.B. Howell, C.M. Baud, R.F. de Boer, D. Pluim, J.H. Beijnen, J.H.M. Schellens, J.-P. Droz, Clin. Cancer Res. 10, 3386 (2004).

    Google Scholar 

  40. X. Lin, Q. Zhang, J.R. Rice, D.R. Stewart, D.P. Nowotnik, S.B. Howell, Eur. J. Cancer 40, 291 (2004).

    Google Scholar 

  41. P. Sengupta, S. Basu, S. Soni, A. Pandey, B. Roy, M.S. Oh, K.T. Chin, A.S. Paraskar, S. Sarangi, Y. Connor, V.S. Sabbisetti, J. Kopparam, A. Kulkarni, K. Muto, C. Amarasiriwardena, I. Jayawardene, N. Lupoli, D.M. Dinulescu, J.V. Bonventre, R.A. Mashelkar, S. Sengupta, Proc. Natl. Acad. Sci. U.S.A. 109, 11294 (2012).

    Google Scholar 

  42. A.S. Paraskar, S. Soni, K.T. Chin, P. Chaudhuri, K.W. Muto, J. Berkowitz, M.W. Handlogten, N.J. Alves, B. Bilgicer, D.M. Dinulescu, R.A. Mashelkar, S. Sengupta, Proc. Natl. Acad. Sci. U.S.A. 107, 12435 (2010).

    Google Scholar 

  43. S.S. Ng, A. Sparreboom, Y. Shaked, C. Lee, S. Man, N. Desai, P. Soon-Shiong, W.D. Figg, R.S. Kerbel, Clin. Cancer Res. 12, 4331 (2006).

    Google Scholar 

  44. P.L. Bedard, A. Di Leo, M.J. Piccart-Gebhart, Nat. Rev. Clin. Oncol. 7, 22 (2010).

    Google Scholar 

  45. Z. Zhang, L. Mei, S.S. Feng, Expert Opin. Drug Deliv. 10, 325 (2013).

    Google Scholar 

  46. K.L. Hennenfent, R. Govindan, Ann. Oncol. 17, 735 (2006).

    Google Scholar 

  47. S. Koudelka, J. Turanek, J. Control. Release 163, 322 (2012).

    Google Scholar 

  48. B.A. Teicher, R.V. Chari, Clin. Cancer Res. 17, 6389 (2011).

    Google Scholar 

  49. A. Beck, J.F. Haeuw, T. Wurch, L. Goetsch, C. Bailly, N. Corvaïa, Discov. Med. 10, 329 (2010).

    Google Scholar 

  50. J. Cheng, K.T. Khin, M.E. Davis, Mol. Pharm. 1, 183 (2004).

    Google Scholar 

  51. J.L. Perry, K.G. Reuter, M.P. Kai, K.P. Herlihy, S.W. Jones, J.C. Luft, M. Napier, J.E. Bear, J.M. DeSimone, Nano Lett. 12, 5304 (2012).

    Google Scholar 

  52. A. Kreso, C.A. O’Brien, P. van Galen, O.I. Gan, F. Notta, A.M.K. Brown, K. Ng, J. Ma, E. Wienholds, C. Dunant, A. Pollett, S. Gallinger, J. McPherson, C.G. Mullighan, D. Shibata, J.E. Dick, Science 339, 543 (2013).

    Google Scholar 

  53. M. Shackleton, E. Quintana, E.R. Fearon, S.J. Morrison, Cell 138, 822 (2009).

    Google Scholar 

  54. V. Almendro, A. Marusyk, K. Polyak, Annu. Rev. Pathol. 8, 277 (2013).

    Google Scholar 

  55. A. Brock, H. Chang, S. Huang, Nat. Rev. Genet. 10, 336 (2009).

    Google Scholar 

  56. A. Marusyk, K. Polyak, Science 339, 528 (2013).

    Google Scholar 

  57. A. Pandey, A. Kulkarni, B. Roy, A. Goldman, S. Sarangi, P. Sengupta, C. Phipps, J. Kopparam, M. Oh, S. Basu, M. Kohandel, S. Sengupta, Cancer Res. (October 11, 2013); http://www.ncbi.nlm.nih.gov/pubmed/24121494.

  58. A.A. Kulkarni, B. Roy, P.S. Rao, G.A. Wyant, A. Mahmoud, M. Ramachandran, P. Sengupta, A. Goldman, V.R. Kotamraju, S. Basu, R.A. Mashelkar, E. Ruoslahti, D.M. Dinulescu, S. Sengupta, Cancer Res. 73 (23), 6987 (2013).

    Google Scholar 

  59. M.J. Lee, A.S. Ye, A.K. Gardino, A.M. Heijink, P.K. Sorger, G. MacBeath, M.B. Yaffe, Cell 149, 780 (2012).

    Google Scholar 

  60. S. Sengupta, D. Eavarone, I. Capila, G. Zhao, N. Watson, T. Kiziltepe, R. Sasisekharan, Nature 436, 568 (2005).

    Google Scholar 

Download references

Acknowledgements

This work is supported by the US Department of Defense (DOD) Breast Cancer Research Program (BCRP) Era of Hope Scholar Award (W81XWH-07–1-0482), DOD Collaborative Innovator Grant (W81XWH-09–700), NIH Grant R01 (1R01CA135242– 01A2), an IUSSTF Joint Center Grant, and an American Lung Association Discovery Grant 481 (LCD-259932-N).

Author information

Authors and Affiliations

  1. Brigham and Women’s Hospital and Harvard Medical School, USA

    Shiladitya Sengupta

Authors
  1. Shiladitya Sengupta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shiladitya Sengupta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sengupta, S. Clinical translational challenges in nanomedicine. MRS Bulletin 39, 259–264 (2014). https://doi.org/10.1557/mrs.2014.29

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1557/mrs.2014.29

Search

Navigation