Tunable CD44-specific cellular retargeting with hyaluronic acid nanoshells
| Autor: | Morten F. Ebbesen, Mikkel Carstensen Gjelstrup, Esben Kjær Unmack Larsen, Birgitte M. Malle, Jan Mollenhauer, Irene Maria Hansen, Malgorzata M. Pakula, Kenneth A. Howard, Pernille Lund Hansen, Morten Tj Olesen |
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| Rok vydání: | 2014 |
| Předmět: |
Cell Survival
Surface Properties Hyaluronic acid Pharmacology toxicology Blotting Western Pharmaceutical Science Nanoparticle Nanotechnology chemistry.chemical_compound Humans Pharmacology (medical) Hyaluronic Acid Particle Size targeting Pharmacology Drug Carriers Microscopy Confocal biology Nanoshells Photoelectron Spectroscopy Organic Chemistry CD44 cd44 Nanoshell Molecular Weight Hyaluronan Receptors chemistry Retargeting biology.protein stealth MCF-7 Cells Molecular Medicine Polystyrenes nanoparticles Biotechnology |
| Zdroj: | Ebbesen, M F, Olesen, M T J, Gjelstrup, M C, Pakula, M M, Larsen, E K, Hansen, I M, Hansen, P L, Mollenhauer, J, Malle, B M & Howard, K 2015, ' Tunable CD44-Specific Cellular Retargeting with Hyaluronic Acid Nanoshells ', Pharmaceutical Research, vol. 32, no. 4, pp. 1462-1474 . https://doi.org/10.1007/s11095-014-1552-7 Ebbesen, M F, Olesen, M T J, Gjelstrup, M C, Pakula, M M, Larsen, E K U, Hansen, I M, Hansen, P L, Mollenhauer, J, Malle, B M & Howard, K A 2015, ' Tunable CD44-Specific Cellular Retargeting with Hyaluronic Acid Nanoshells ', Pharmaceutical Research, vol. 32, no. 4, pp. 1462-1474 . https://doi.org/10.1007/s11095-014-1552-7 |
| ISSN: | 1573-904X |
| DOI: | 10.1007/s11095-014-1552-7 |
| Popis: | 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 non-constricted 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. |
| Databáze: | OpenAIRE |
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