Preparation of Hyaluronic Acid-Based Nanoparticles for Macrophage-Targeted MicroRNA Delivery and Transfection

  • Neha N. ParayathEmail author
  • Mansoor M. Amiji
Part of the Methods in Molecular Biology book series (MIMB, volume 2118)


Skewing the macrophage polarity to achieve a favorable phenotype is a recently investigated therapeutic strategy in multiple disease/dysfunctional conditions such as inflammation, tumors, autoimmune disorders, and tissue repairs. However, delivering the therapeutic agent specifically to the macrophages has been a challenge in this field. Here, we describe the synthesis of hyaluronic acid (HA)-based nanoparticles for targeting CD44 receptors on the macrophages. The HA backbone is modified with cationic polyethyleneimine (PEI) for efficient encapsulation of microRNA into the self-assembling nanoparticles for targeted delivery to macrophages.

Key words

Hyaluronic acid nanoparticles CD44 Macrophages Poly(ethyleneimine) Targeted delivery M1 and M2 polarization MicroRNA-125b 



The manuscript was edited by Enrico Ferrari and Mikhail Soloviev. Financial support for this work was provided by the United States National Cancer Institute of the National Institute of Health through grants R21-CA179652 and R56-CA198492, and the Northeastern University-Dana Farber Cancer Center Joint Program on Cancer Drug Development.


  1. 1.
    Komohara Y, Fujiwara Y, Ohnishi K et al (2016) Tumor-associated macrophages: potential therapeutic targets for anti-cancer therapy. Adv Drug Deliv Rev 99:180–185CrossRefGoogle Scholar
  2. 2.
    Chawla A, Nguyen KD, Goh YPS (2011) Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol 11:738–749CrossRefGoogle Scholar
  3. 3.
    Wynn TA, Vannella KM (2016) Macrophages in tissue repair, regeneration, and fibrosis. Immunity 44:450–462CrossRefGoogle Scholar
  4. 4.
    Ginhoux F, Schultze JL, Murray PJ et al (2016) New insights into the multidimensional concept of macrophage ontogeny, activation and function. Nat Immunol 17:34–40CrossRefGoogle Scholar
  5. 5.
    Shapouri-Moghaddam A, Mohammadian S, Vazini H et al (2018) Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 233:6425–6440CrossRefGoogle Scholar
  6. 6.
    Chellat F, Merhi Y, Moreau A et al (2005) Therapeutic potential of nanoparticulate systems for macrophage targeting. Biomaterials 26:7260–7275CrossRefGoogle Scholar
  7. 7.
    Zanganeh S, Hutter G, Spitler R et al (2016) Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues. Nat Nanotechnol 11:986–994CrossRefGoogle Scholar
  8. 8.
    Hatami E, Mu Y, Shields DN et al (2019) Mannose-decorated hybrid nanoparticles for enhanced macrophage targeting. Biochem Biophys Rep 17:197–207PubMedPubMedCentralGoogle Scholar
  9. 9.
    Parayath NN, Amiji MM (2017) Therapeutic targeting strategies using endogenous cells and proteins. J Control Release 258:81–94CrossRefGoogle Scholar
  10. 10.
    Bagalkot V, Badgeley MA, Kampfrath T et al (2015) Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals. J Control Release 217:243–255CrossRefGoogle Scholar
  11. 11.
    Tokutome M, Matoba T, Nakano Y et al (2018) Peroxisome proliferator-activated receptor-gamma targeting nanomedicine promotes cardiac healing after acute myocardial infarction by skewing monocyte/macrophage polarization in preclinical animal models. Cardiovasc Res 115:419–431CrossRefGoogle Scholar
  12. 12.
    Parayath NN, Nehoff H, Müller P et al (2015) Styrene maleic acid micelles as a nanocarrier system for oral anticancer drug delivery—dual uptake through enterocytes and M-cells. Int J Nanomedicine 10:4653–4667PubMedPubMedCentralGoogle Scholar
  13. 13.
    Tran TH, Krishnan S, Amiji MM (2016) MicroRNA-223 induced repolarization of peritoneal macrophages using CD44 targeting hyaluronic acid nanoparticles for anti-inflammatory effects. PLoS One 11:e0152024CrossRefGoogle Scholar
  14. 14.
    Parayath NN, Parikh A, Amiji MM (2018) Repolarization of tumor-associated macrophages in a genetically engineered nonsmall cell lung cancer model by Intraperitoneal Administration of Hyaluronic Acid-Based Nanoparticles Encapsulating MicroRNA-125b. Nano Lett 18:3571–3579CrossRefGoogle Scholar
  15. 15.
    Ganesh S, Iyer AK, Morrissey DV et al (2013) Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors. Biomaterials 34:3489–3502CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, School of PharmacyNortheastern UniversityBostonUSA
  2. 2.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA

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