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Monoclonal Antibody-Conjugated Dendritic Nanostructures for siRNA Delivery

  • Hitesh KulhariEmail author
  • Ashok K. Jangid
  • David J. Adams
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1974)

Abstract

Small interfering RNA (siRNA) is a promising tool for gene therapy-based disease treatments. However, delivery of siRNA to the target cells requires a specific and reliable carrier system. Herein we describe a targeted carrier system that can deliver siRNA to cancer cells overexpressing the human epidermal growth factor 2 (HER2) receptor. Trastuzumab-conjugated poly(amido)amine dendrimers can be synthesized using the protocols described here.

Keywords

siRNA delivery Dendrimers Trastuzumab Bioconjugation HER2 receptors 

Notes

Acknowledgments

H.K. acknowledges the Department of Science and Technology, New Delhi, for INSPIRE Faculty Award. A.K.J. acknowledges the University Grants Commission, New Delhi, for Ph.D. scholarship.

References

  1. 1.
    Xin Y, Huang M, Guo MM et al (2017) Nano-based delivery of RNAi in cancer therapy. Mol Cancer 16:134CrossRefGoogle Scholar
  2. 2.
    Fellmann C, Lowe SW (2014) Stable RNA interference rules for silencing. Nat Cell Biol 16(1):10–18CrossRefGoogle Scholar
  3. 3.
    Scherman D, Rousseau A, Bigey P et al (2017) Genetic pharmacology: progresses in siRNA delivery and therapeutic applications. Gene Ther 24:151–156CrossRefGoogle Scholar
  4. 4.
    Haussecker D (2014) Current issues of RNAi therapeutics delivery and development. J Control Release 195:49–54CrossRefGoogle Scholar
  5. 5.
    Mizrahy S, Hazan-Halevy I, Dammes N et al (2017) Current progress in non-viral RNAi-based delivery strategies to lymphocytes. Mol Ther 25:1–10CrossRefGoogle Scholar
  6. 6.
    Wang J, Lu Z, Wientjes MG et al (2010) Delivery of siRNA therapeutics: barriers and carriers. AAPS J 12:492–503CrossRefGoogle Scholar
  7. 7.
    Ozpolat B, Sood AK, Lopez-Berestein G (2014) Liposomal siRNA nanocarriers for cancer therapy. Adv Drug Deliv Rev 66:110–116CrossRefGoogle Scholar
  8. 8.
    Wu SY, Lopez-Berestein G, Calin GA et al (2014) RNAi therapies: drugging the undruggable. Sci Transl Med 6(240):240ps7CrossRefGoogle Scholar
  9. 9.
    Yang J, Zhang Q, Chang H, Cheng Y (2015) Surface-engineered dendrimers in gene delivery. Chem Rev 115:5274–5300CrossRefGoogle Scholar
  10. 10.
    Biswas S, Torchilin VP (2013) Dendrimers for siRNA delivery. Pharmaceuticals 6:161–183CrossRefGoogle Scholar
  11. 11.
    Zhou J, Wu J, Hafdi N et al (2006) PAMAM dendrimers for efficient siRNA delivery and potent gene silencing. Chem Commun (Camb) 22:2362–2364CrossRefGoogle Scholar
  12. 12.
    Senkusa E, Cardosob F, Pagani O (2014) Time for more optimism in metastatic breast cancer? Cancer Treat Rev 40:220–228CrossRefGoogle Scholar
  13. 13.
    Sampathkumar SG, Yarema KJ (2007) Dendrimers in cancer treatment and diagnosis. In: Kumar CSSR (ed) Nanotechnologies for the life sciences, vol 7. Wiley-VCH, WeinheimGoogle Scholar
  14. 14.
    Figueroa-Magalhães MC, Jelovac D, Connolly RM, Wolff AC (2014) Treatment of HER2-positive breast cancer. Breast 23:128–136CrossRefGoogle Scholar
  15. 15.
    Kulhari H, Pooja D, Rompicharla SVK et al (2015) Biomedical applications of Trastuzumab: as a therapeutic agent and a targeting ligand. Med Res Rev 35:849–876CrossRefGoogle Scholar
  16. 16.
    Kulhari H, Pooja D, Shrivastava S et al (2015) Trastuzumab-grafted PAMAM dendrimers for the selective delivery of anticancer drugs to HER2-positive breast cancer. Sci Rep 6:23179CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hitesh Kulhari
    • 1
    Email author
  • Ashok K. Jangid
    • 1
  • David J. Adams
    • 2
  1. 1.School of Nano SciencesCentral University of GujaratGandhinagarIndia
  2. 2.Illawarra Health and Medical Research Institute (IHMRI)University of WollongongWollongongAustralia

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