Tunable CD44-specific cellular retargeting with hyaluronic acid nanoshells

Morten F. Ebbesen, Morten T. J. Olesen, Mikkel C. Gjelstrup, Malgorzata M. Pakula, Esben Kjær Unmack Larsen, Irene M. Hansen, Birgitte Mølholm Malle, Pernille L. Hansen, Jan Mollenhauer, Birgitte M. Malle, Ken Howard

    Research output: Contribution to journalJournal articleResearchpeer-review


    Purpose In this work we specifically investigate the molecular weight (Mw) dependent combinatorial properties of hyaluronic acid (HA) for exhibiting stealth and targeting properties using different Mw HA nanoshells to tune nanoparticle retargeting to CD44-expressing cancer cells. Methods HA of different Mw was covalently grafted onto model polystyrene nanoparticles and advanced surface analysis by X-ray photoelectron spectroscopy performed to quantify and evaluate the effect of the coating procedure. Specific CD44-mediated retargeting was investigated by flow cytometry and confocal microscopy using isogenic D44-deficient and CD44-expressing MCF-7 breast adenocarcinoma cells. Results Surface analysis demonstrated effective surface coating with 33, 260 and 900 kDa HA resulting in increased colloidal stability and highly negative surface charge due to presentation of up to 4.7% carboxyl groups that indicates an extended and nonconstricted HA polymer surface. Reduced non-specific particle interaction in CD44- cells was shown for all HA nanoshells but CD44-dependent cellular retargeting and internalization in CD44+ cells was highly dependent on the coating HA Mw properties.
    Conclusion The combination of advanced surface characterization and evaluation of particle interactions in isogenic cells with and without CD44 receptor demonstrates direct evidence for the dual capacity of HA for stealth and CD44-mediated retargeting tunable by the HA molecular weight.
    Original languageEnglish
    JournalPharmaceutical Research
    Issue number4
    Pages (from-to)1462-1474
    Publication statusPublished - 2014


    • Hyaluronic acid
    • Stealth
    • Targeting
    • cd44
    • Nanoparticles


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