Skip to main content
Log in

Fabrication of Low-Generation Dendrimers into Nanostructures for Efficient and Nontoxic Gene Delivery

  • Review
  • Published:
Topics in Current Chemistry Aims and scope Submit manuscript

Abstract

Dendrimers with well-defined molecular structure and high monodispersity have gained tremendous interest in gene delivery. However, current gene carriers based on dendrimers are either not effective or are too toxic on the transfected cells. The efficacy and cytotoxicity of dendrimers are strongly correlated with their molecular weight or generation. High-generation dendrimers are reported with relatively high transfection efficacy but serious cytotoxicity due to the excess positive charges on the polymers, while low-generation dendrimers with minimal toxicity have poor polyplex stability and thus weak transfection efficacy. To break up the correlation between efficacy and toxicity, low-generation dendrimers were fabricated into various nanostructures by several strategies to improve their gene-binding capacity, polyplex stability, and transfection efficacy without inducing additional toxicity. In this review article, we will highlight recent advances in the development of assembled dendrimer nanostructures for efficient and non-toxic gene delivery. Specifically, the principles and strategies in the fabrication of dendrimer nanostructures are intensively reviewed.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Kannan RM, Nance E, Kannan S, Tomalia DA (2014) J Intern Med 276:579

    Article  CAS  Google Scholar 

  2. Svenson S, Tomalia DA (2005) Adv Drug Deliv Rev 57:2106

    Article  CAS  Google Scholar 

  3. Tomalia DA, Khanna SN (2016) Chem Rev 116:2705

    Article  CAS  Google Scholar 

  4. Esfand R, Tomalia DA (2001) Drug Discov Today 6:427

    Article  CAS  Google Scholar 

  5. Shao N, Dai T, Liu Y, Li L, Cheng Y (2014) Soft Matter 10:9153

    Article  CAS  Google Scholar 

  6. Haensler J, Szoka FC Jr (1993) Bioconjug Chem 4:372

    Article  CAS  Google Scholar 

  7. Kukowska-Latallo JF, Bielinska AU, Johnson J, Spindler R, Tomalia DA, Baker JR Jr (1996) Proc Natl Acad Sci USA 93:4897

    Article  CAS  Google Scholar 

  8. Yang J, Zhang Q, Chang H, Cheng Y (2015) Chem Rev 115:5274

    Article  CAS  Google Scholar 

  9. Hu J, Hu K, Cheng Y (2016) Acta Biomater 35:1

    Article  Google Scholar 

  10. Wang H, Huang Q, Chang H, Xiao J, Cheng Y (2016) Biomater Sci 4:375

    Article  CAS  Google Scholar 

  11. Dufes C, Uchegbu IF, Schatzlein AG (2005) Adv Drug Deliv Rev 57:2177

    Article  CAS  Google Scholar 

  12. Mastrobattista E, Hennink WE (2011) Nat Mater 11:10

    Article  Google Scholar 

  13. Nam HY, Nam K, Lee M, Kim SW, Bull DA (2012) J Control Release 160:592

    Article  CAS  Google Scholar 

  14. Nam K, Jung S, Nam JP, Kim SW (2015) J Control Release 220:447

    Article  CAS  Google Scholar 

  15. Pan S, Cao D, Huang H, Yi W, Qin L, Feng M (2013) Macromol Biosci 13:422

    Article  CAS  Google Scholar 

  16. Zeng X, Pan S, Li J, Wang C, Wen Y, Wu H, Wang C, Wu C, Feng M (2011) Nanotechnology 22:375102

    Article  Google Scholar 

  17. Zhou J, Liu J, Cheng CJ, Patel TR, Weller CE, Piepmeier JM, Jiang Z, Saltzman WM (2011) Nat Mater 11:82

    Article  Google Scholar 

  18. Breunig M, Lungwitz U, Liebl R, Goepferich A (2007) Proc Natl Acad Sci USA 104:14454

    Article  CAS  Google Scholar 

  19. Gosselin MA, Guo W, Lee RJ (2001) Bioconjug Chem 12:989

    Article  CAS  Google Scholar 

  20. Liu C, Shao N, Wang Y, Cheng Y (2016) Adv Healthc Mater 5:584

    Article  CAS  Google Scholar 

  21. Liu H, Wang H, Yang W, Cheng Y (2012) J Am Chem Soc 134:17680

    Article  CAS  Google Scholar 

  22. Yu T, Liu X, Bolcato-Bellemin AL, Wang Y, Liu C, Erbacher P, Qu F, Rocchi P, Behr JP, Peng L (2012) Angew Chem Int Ed Engl 51:8478

    Article  CAS  Google Scholar 

  23. Liu X, Zhou J, Yu T, Chen C, Cheng Q, Sengupta K, Huang Y, Li H, Liu C, Wang Y, Posocco P, Wang M, Cui Q, Giorgio S, Fermeglia M, Qu F, Pricl S, Shi Y, Liang Z, Rocchi P, Rossi JJ, Peng L (2014) Angew Chem Int Ed Engl 53:11822

    Article  CAS  Google Scholar 

  24. Wang H, Wang Y, Wang Y, Hu J, Li T, Liu H, Zhang Q, Cheng Y (2015) Angew Chem Int Ed Engl 54:11647

    Article  CAS  Google Scholar 

  25. Xu X, Jian Y, Li Y, Zhang X, Tu Z, Gu Z (2014) ACS Nano 8:9255

    Article  CAS  Google Scholar 

  26. Dong R, Zhou Y, Zhu X (2014) Acc Chem Res 47:2006

    Article  CAS  Google Scholar 

  27. Shao N, Dai T, Liu Y, Cheng Y (2015) Chem Commun (Camb) 51:9741

    Article  CAS  Google Scholar 

  28. Shao N, Liu Y, Dai T, Cheng Y (2015) J Control Release 213:e82

    Article  Google Scholar 

  29. Wei T, Chen C, Liu J, Liu C, Posocco P, Liu X, Cheng Q, Huo S, Liang Z, Fermeglia M, Pricl S, Liang XJ, Rocchi P, Peng L (2015) Proc Natl Acad Sci USA 112:2978

    Article  CAS  Google Scholar 

  30. Liu X, Liu C, Zhou J, Chen C, Qu F, Rossi JJ, Rocchi P, Peng L (2015) Nanoscale 7:3867

    Article  CAS  Google Scholar 

  31. Kono K, Ikeda R, Tsukamoto K, Yuba E, Kojima C, Harada A (2012) Bioconjug Chem 23:871

    Article  CAS  Google Scholar 

  32. Malhotra S, Bauer H, Tschiche A, Staedtler AM, Mohr A, Calderon M, Parmar VS, Hoeke L, Sharbati S, Einspanier R, Haag R (2012) Biomacromol 13:3087

    Article  CAS  Google Scholar 

  33. Takahashi T, Kojima C, Harada A, Kono K (2007) Bioconjug Chem 18:1349

    Article  CAS  Google Scholar 

  34. Kono K, Murakami E, Hiranaka Y, Yuba E, Kojima C, Harada A, Sakurai K (2011) Angew Chem Int Ed Engl 50:6332

    Article  CAS  Google Scholar 

  35. Takahashi T, Harada A, Emi N, Kono K (2005) Bioconjug Chem 16:1160

    Article  CAS  Google Scholar 

  36. Takahashi T, Kono K, Itoh T, Emi N, Takagishi T (2003) Bioconjug Chem 14:764

    Article  CAS  Google Scholar 

  37. Harada A, Kimura Y, Kojima C, Kono K (2010) Biomacromol 11:1036

    Article  CAS  Google Scholar 

  38. Yang B, Dong X, Lei Q, Zhuo R, Feng J, Zhang X (2015) ACS Appl Mater Interfaces 7:22084

    Article  CAS  Google Scholar 

  39. Jones SP, Gabrielson NP, Wong CH, Chow HF, Pack DW, Posocco P, Fermeglia M, Pricl S, Smith DK (2011) Mol Pharm 8:416

    Article  CAS  Google Scholar 

  40. Chen C, Posocco P, Liu X, Cheng Q, Laurini E, Zhou J, Liu C, Wang Y, Tang J, Col VD, Yu T, Giorgio S, Fermeglia M, Qu F, Liang Z, Rossi JJ, Liu M, Rocchi P, Pricl S, Peng L (2016) Small 12:3604

    Article  Google Scholar 

  41. Marquez-Miranda V, Araya-Duran I, Camarada MB, Comer J, Valencia-Gallegos JA, Gonzalez-Nilo FD (2016) Sci Rep 6:29436

    Article  CAS  Google Scholar 

  42. Yuba E, Nakajima Y, Tsukamoto K, Iwashita S, Kojima C, Harada A, Kono K (2012) J Control Release 160:552

    Article  CAS  Google Scholar 

  43. Ewert KK, Evans HM, Zidovska A, Bouxsein NF, Ahmad A, Safinya CR (2006) J Am Chem Soc 128:3998

    Article  CAS  Google Scholar 

  44. Zhang Y, Chen J, Xiao C, Li M, Tian H, Chen X (2013) Biomacromol 14:4289

    Article  CAS  Google Scholar 

  45. Semple SC, Akinc A, Chen J, Sandhu AP, Mui BL, Cho CK, Sah DW, Stebbing D, Crosley EJ, Yaworski E, Hafez IM, Dorkin JR, Qin J, Lam K, Rajeev KG, Wong KF, Jeffs LB, Nechev L, Eisenhardt ML, Jayaraman M, Kazem M, Maier MA, Srinivasulu M, Weinstein MJ, Chen Q, Alvarez R, Barros SA, De S, Klimuk SK, Borland T, Kosovrasti V, Cantley WL, Tam YK, Manoharan M, Ciufolini MA, Tracy MA, de Fougerolles A, MacLachlan I, Cullis PR, Madden TD, Hope MJ (2010) Nat Biotechnol 28:172

    Article  CAS  Google Scholar 

  46. Jones SP, Gabrielson NP, Pack DW, Smith DK (2008) Chem Commun 39:4700

    Article  Google Scholar 

  47. Morales-Sanfrutos J, Megia-Fernandez A, Hernandez-Mateo F, Giron-Gonzalez MD, Salto-Gonzalez R, Santoyo-Gonzalez F (2011) Org Biomol Chem 9:851

    Article  CAS  Google Scholar 

  48. Barnard A, Posocco P, Pricl S, Calderon M, Haag R, Hwang ME, Shum VW, Pack DW, Smith DK (2011) J Am Chem Soc 133:20288

    Article  CAS  Google Scholar 

  49. Kim JY, Ryu JH, Hyun H, Kim HA, Choi JS, Yun Lee D, Rhim T, Park JH, Lee M (2012) J Drug Target 20:667

    Article  CAS  Google Scholar 

  50. Xiao Q, Rubien JD, Wang Z, Reed EH, Hammer DA, Sahoo D, Heiney PA, Yadavalli SS, Goulian M, Wilner SE, Baumgart T, Vinogradov SA, Klein ML, Percec V (2016) J Am Chem Soc 138:12655

    Article  CAS  Google Scholar 

  51. Percec V, Glodde M, Johansson G, Balagurusamy VS, Heiney PA (2003) Angew Chem Int Ed Engl 42:4338

    Article  CAS  Google Scholar 

  52. Tomalia DA (2003) Nat Mater 2:711

    Article  CAS  Google Scholar 

  53. Wang H, Wang Y, Liu H, Zhang Q, Cheng Y (2015) J Control Release 213:e42

    Article  Google Scholar 

  54. He B, Wang Y, Shao N, Chang H, Cheng Y (2015) Acta Biomater 22:111

    Article  CAS  Google Scholar 

  55. Wang M, Liu H, Li L, Cheng Y (2014) Nat Commun 5:3053

    Google Scholar 

  56. Liu H, Wang Y, Wang M, Xiao J, Cheng Y (2014) Biomaterials 35:5407

    Article  CAS  Google Scholar 

  57. Wang M, Cheng Y (2014) Biomaterials 35:6603

    Article  CAS  Google Scholar 

  58. Wang M, Cheng Y (2016) Acta Biomater 46:204

    Article  CAS  Google Scholar 

  59. Shen W, Wang H, Linghu Y, Lv J, Chang H, Cheng Y (2016) J. Mater. Chem. B 4:6468

    Article  CAS  Google Scholar 

  60. Wang H, Hu J, Cai X, Xiao J, Cheng Y (2016) Polym Chem 7:2319

    Article  CAS  Google Scholar 

  61. Wang X, Cai X, Hu J, Shao N, Wang F, Zhang Q, Xiao J, Cheng Y (2013) J Am Chem Soc 135:9805

    Article  CAS  Google Scholar 

  62. Kim ST, Chompoosor A, Yeh YC, Agasti SS, Solfiell DJ, Rotello VM (2012) Small 8:3253

    Article  CAS  Google Scholar 

  63. Radu DR, Lai CY, Jeftinija K, Rowe EW, Jeftinija S, Lin VS (2004) J Am Chem Soc 126:13216

    Article  CAS  Google Scholar 

  64. Yu C, Qian L, Ge J, Fu J, Yuan P, Yao SC, Yao SQ (2016) Angew Chem Int Ed Engl 55:9272

    Article  CAS  Google Scholar 

  65. Chang FP, Chen YP, Mou CY (2014) Small 10:4785

    Article  CAS  Google Scholar 

  66. Wu M, Meng Q, Chen Y, Du Y, Zhang L, Li Y, Zhang L, Shi J (2015) Adv Mater 27:215

    Article  CAS  Google Scholar 

  67. Zhou Z, Wang Y, Yan Y, Zhang Q, Cheng Y (2016) ACS Nano 10:4863

    Article  CAS  Google Scholar 

  68. Liu H, Xu Y, Wen S, Chen Q, Zheng L, Shen M, Zhao J, Zhang G, Shi X (2013) Chemistry 19:6409

    Article  CAS  Google Scholar 

  69. Kong L, Alves CS, Hou W, Qiu J, Mohwald H, Tomas H, Shi X (2015) ACS Appl Mater Interfaces 7:4833

    Article  CAS  Google Scholar 

  70. Shan Y, Luo T, Peng C, Sheng R, Cao A, Cao X, Shen M, Guo R, Tomas H, Shi X (2012) Biomaterials 33:3025

    Article  CAS  Google Scholar 

  71. Chen AM, Taratula O, Wei D, Yen HI, Thomas T, Thomas TJ, Minko T, He H (2010) ACS Nano 4:3679

    Article  CAS  Google Scholar 

  72. Kostiainen MA, Szilvay GR, Lehtinen J, Smith DK, Linder MB, Urtti A, Ikkala O (2007) ACS Nano 1:103

    Article  CAS  Google Scholar 

  73. Deng J, Zhou Y, Xu B, Mai K, Deng Y, Zhang LM (2011) Biomacromol 12:642

    Article  CAS  Google Scholar 

  74. Mai K, Lin J, Zhuang B, Li X, Zhang LM (2015) Int J Biol Macromol 79:209

    Article  CAS  Google Scholar 

  75. Huang H, Cao D, Qin L, Tian S, Liang Y, Pan S, Feng M (2014) Mol Pharm 11:2323

    Article  CAS  Google Scholar 

  76. Xue YN, Liu M, Peng L, Huang SW, Zhuo RX (2010) Macromol Biosci 10:404

    Article  CAS  Google Scholar 

  77. Zeng H, Little HC, Tiambeng TN, Williams GA, Guan Z (2013) J Am Chem Soc 135:4962

    Article  CAS  Google Scholar 

  78. Gossl I, Shu L, Schluter AD, Rabe JP (2002) J Am Chem Soc 124:6860

    Article  Google Scholar 

  79. Wu HM, Pan SR, Chen MW, Wu Y, Wang C, Wen YT, Zeng X, Wu CB (2011) Biomaterials 32:1619

    Article  CAS  Google Scholar 

  80. Ariaee FM, Hashemi M, Farzad SA, Abnous K, Ramezani M (2016) Iran J Basic Med Sci 19:1096

    Google Scholar 

  81. Li CY, Wang HJ, Cao JM, Zhang J, Yu XQ (2014) Eur J Med Chem 87:413

    Article  CAS  Google Scholar 

  82. Cai X, Jin R, Wang J, Yue D, Jiang Q, Wu Y, Gu Z (2016) ACS Appl Mater Interfaces 8:5821

    Article  CAS  Google Scholar 

  83. Huang CH, Nwe K, Al Zaki A, Brechbiel MW, Tsourkas A (2012) ACS Nano 6:9416

    Article  CAS  Google Scholar 

  84. Jia HZ, Zhang W, Zhu JY, Yang B, Chen S, Chen G, Zhao YF, Feng J, Zhang XZ (2015) J Control Release 216:9

    Article  CAS  Google Scholar 

  85. Jia HZ, Zhang W, Wang XL, Yang B, Chen WH, Chen S, Chen G, Zhao YF, Zhuo RX, Feng J, Zhang XZ (2015) Biomater Sci 3:1066

    Article  CAS  Google Scholar 

  86. Zhu JY, Zeng X, Qin SY, Wan SS, Jia HZ, Zhuo RX, Feng J, Zhang XZ (2016) Biomaterials 83:79

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We thank financial supports from the National Natural Science Foundation of China (No. 81601587, No. 21474030) and the Science and Technology Commission of Shanghai Municipality (17XD1401600 and 148014518).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yiyun Cheng.

Additional information

This article is part of the Topical Collection “Polymeric Gene Delivery Systems”; edited by Yiyun Cheng.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Chang, H., Zhang, Q. et al. Fabrication of Low-Generation Dendrimers into Nanostructures for Efficient and Nontoxic Gene Delivery. Top Curr Chem (Z) 375, 62 (2017). https://doi.org/10.1007/s41061-017-0151-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s41061-017-0151-6

Keywords

Navigation