Advertisement

Multifunctional Nanodelivery Platform for Maximizing Nucleic Acids Combination Therapy

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2115)

Abstract

The silencing of an oncogene with a small interfering RNA (siRNA) is a promising way for cancer therapy. Its efficacy can be further enhanced by integrating with other therapeutics; however, transporting siRNA and other active ingredients to the same location at the same time is challenging. Here, we report a novel multifunctional nanodelivery platform by sequentially layering several functional ingredients, such as siRNAs, microRNAs, peptides, and targeting ligands, onto a core through charge–charge interaction. The prepared nanovectors effectively and programmably delivered multiple active components to maximize therapeutic combination with minimal off-targeting effects.

Key words

Small interfering RNA KLA peptide Hyaluronic acid microRNA Nucleic acids Layer-by-layer Gold nanoparticles Poly-l-lysine Electrostatic interactions Combination therapy 

Notes

Acknowledgments

This study was supported in part by NIH CA135312 and DOD W81XWH-11-1-0442.

References

  1. 1.
    Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498CrossRefGoogle Scholar
  2. 2.
    Bumcrot D, Manoharan M, Koteliansky V, Sah DW (2006) RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol 2:711–719CrossRefGoogle Scholar
  3. 3.
    Burnett JC, Rossi JJ (2012) RNA-based therapeutics: current progress and future prospects. Chem Biol 19:60–71CrossRefGoogle Scholar
  4. 4.
    Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355CrossRefGoogle Scholar
  5. 5.
    Garzon R, Marcucci G, Croce CM (2010) Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov 9:775–789CrossRefGoogle Scholar
  6. 6.
    Conde J, Artzi N (2015) Are RNAi and miRNA therapeutics truly dead? Trends Biotechnol 33:141–144CrossRefGoogle Scholar
  7. 7.
    Lee SK, Han MS, Asokan S, Tung CH (2011) Effective gene silencing by multilayered siRNA-coated gold nanoparticles. Small 7:364–370CrossRefGoogle Scholar
  8. 8.
    Peyratout CS, Dahne L (2004) Tailor-made polyelectrolyte microcapsules: from multilayers to smart containers. Angew Chem Int Ed Engl 43:3762–3783CrossRefGoogle Scholar
  9. 9.
    Jewell CM, Lynn DM (2008) Multilayered polyelectrolyte assemblies as platforms for the delivery of DNA and other nucleic acid-based therapeutics. Adv Drug Deliv Rev 60:979–999CrossRefGoogle Scholar
  10. 10.
    Reum N, Fink-Straube C, Klein T, Hartmann RW, Lehr CM, Schneider M (2010) Multilayer coating of gold nanoparticles with drug-polymer coadsorbates. Langmuir 26:16901–16908CrossRefGoogle Scholar
  11. 11.
    Chanana M, Gliozzi A, Diaspro A, Chodnevskaja I, Huewel S, Moskalenko V et al (2005) Interaction of polyelectrolytes and their composites with living cells. Nano Lett 5:2605–2612CrossRefGoogle Scholar
  12. 12.
    Daniel MC, Astruc D (2004) Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem Rev 104:293–346CrossRefGoogle Scholar
  13. 13.
    Jans H, Jans K, Lagae L, Borghs G, Maes G, Huo Q (2010) Poly(acrylic acid)-stabilized colloidal gold nanoparticles: synthesis and properties. Nanotechnology 21:455702CrossRefGoogle Scholar
  14. 14.
    Liz-Marzan LM (2006) Tailoring surface plasmons through the morphology and assembly of metal nanoparticles. Langmuir 22:32–41CrossRefGoogle Scholar
  15. 15.
    Ramchandani D, Lee SK, Yomtoubian S, Han MS, Tung CH, Mittal V (2019) Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis. Mol Cancer Ther 18:579–591CrossRefGoogle Scholar
  16. 16.
    Ryu S, McDonnell K, Choi H, Gao D, Hahn M, Joshi N et al (2013) Suppression of miRNA-708 by polycomb group promotes metastases by calcium-induced cell migration. Cancer Cell 23:63–76CrossRefGoogle Scholar
  17. 17.
    Wang S, Shi Z, Liu W, Jules J, Feng X (2006) Development and validation of vectors containing multiple siRNA expression cassettes for maximizing the efficiency of gene silencing. BMC Biotechnol 6:50CrossRefGoogle Scholar
  18. 18.
    Peter ME (2010) Targeting of mRNAs by multiple miRNAs: the next step. Oncogene 29:2161–2164CrossRefGoogle Scholar
  19. 19.
    Lee SK, Tung CH (2013) A fabricated siRNA nanoparticle for ultra-long gene silencing. Adv Funct Mater 23:3488–3493CrossRefGoogle Scholar
  20. 20.
    Nishimura M, Jung EJ, Shah MY, Lu C, Spizzo R, Shimizu M et al (2013) Therapeutic synergy between microRNA and siRNA in ovarian cancer treatment. Cancer Discov 3:1302–1315CrossRefGoogle Scholar
  21. 21.
    Xue W, Dahlman JE, Tammela T, Khan OF, Sood S, Dave A et al (2014) Small RNA combination therapy for lung cancer. Proc Natl Acad Sci U S A 111:E3553–E3561CrossRefGoogle Scholar
  22. 22.
    Reis-Filho JS, Steele D, Di Palma S, Jones RL, Savage K, James M et al (2006) Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue. Mod Pathol 19:307–319CrossRefGoogle Scholar
  23. 23.
    Vanhecke E, Adriaenssens E, Verbeke S, Meignan S, Germain E, Berteaux N et al (2011) Brain-derived neurotrophic factor and neurotrophin-4/5 are expressed in breast cancer and can be targeted to inhibit tumor cell survival. Clin Cancer Res 17:1741–1752CrossRefGoogle Scholar
  24. 24.
    Zuo QF, Zhang R, Li BS, Zhao YL, Zhuang Y, Yu T et al (2015) MicroRNA-141 inhibits tumor growth and metastasis in gastric cancer by directly targeting transcriptional co-activator with PDZ-binding motif, TAZ. Cell Death Dis 6:e1623CrossRefGoogle Scholar
  25. 25.
    Finlay-Schultz J, Cittelly DM, Hendricks P, Patel P, Kabos P, Jacobsen BM et al (2015) Progesterone downregulation of miR-141 contributes to expansion of stem-like breast cancer cells through maintenance of progesterone receptor and Stat5a. Oncogene 34:3676–3687CrossRefGoogle Scholar
  26. 26.
    Lee SK, Law B, Tung CH (2017) Versatile nanodelivery platform to maximize siRNA combination therapy. Macromol Biosci 17:1600294CrossRefGoogle Scholar
  27. 27.
    Javadpour MM, Juban MM, Lo WC, Bishop SM, Alberty JB, Cowell SM et al (1996) De novo antimicrobial peptides with low mammalian cell toxicity. J Med Chem 39:3107–3113CrossRefGoogle Scholar
  28. 28.
    Ellerby HM, Arap W, Ellerby LM, Kain R, Andrusiak R, Rio GD et al (1999) Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med 5:1032–1038CrossRefGoogle Scholar
  29. 29.
    Agemy L, Friedmann-Morvinski D, Kotamraju VR, Roth L, Sugahara KN, Girard OM et al (2011) Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma. Proc Natl Acad Sci U S A 108:17450–17455CrossRefGoogle Scholar
  30. 30.
    Cieslewicz M, Tang J, Yu JL, Cao H, Zavaljevski M, Motoyama K et al (2013) Targeted delivery of proapoptotic peptides to tumor-associated macrophages improves survival. Proc Natl Acad Sci U S A 110:15919–15924CrossRefGoogle Scholar
  31. 31.
    Chen WH, Xu XD, Luo GF, Jia HZ, Lei Q, Cheng SX et al (2013) Dual-targeting pro-apoptotic peptide for programmed cancer cell death via specific mitochondria damage. Sci Rep 3:3468CrossRefGoogle Scholar
  32. 32.
    Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61:1303–1313CrossRefGoogle Scholar
  33. 33.
    Oh EJ, Park K, Kim KS, Kim J, Yang JA, Kong JH et al (2010) Target specific and long-acting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives. J Control Release 141:2–12CrossRefGoogle Scholar
  34. 34.
    Dreaden EC, Morton SW, Shopsowitz KE, Choi JH, Deng ZJ, Cho NJ et al (2014) Bimodal tumor-targeting from microenvironment responsive hyaluronan layer-by-layer (LbL) nanoparticles. ACS Nano 8:8374–8382CrossRefGoogle Scholar
  35. 35.
    Lee SK, Mortensen LJ, Lin CP, Tung CH (2014) An authentic imaging probe to track cell fate from beginning to end. Nat Commun 5:5216CrossRefGoogle Scholar
  36. 36.
    Lee SK, Han MS, Tung CH (2012) Layered nanoprobe for long-lasting fluorescent cell label. Small 8:3315–3320CrossRefGoogle Scholar
  37. 37.
    Lee SK, Tung CH (2016) siRNA nanoparticles for ultra-long gene silencing in vivo. Methods Mol Biol 1372:113–120CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Department of Radiology, Weill Cornell MedicineMolecular Imaging Innovations InstituteNew YorkUSA

Personalised recommendations