Hyaluronan Polymer Length, Grafting Density, and Surface Poly(ethylene glycol) Coating Influence in Vivo Circulation and Tumor Targeting of Hyaluronan-Grafted Liposomes
| العنوان: | Hyaluronan Polymer Length, Grafting Density, and Surface Poly(ethylene glycol) Coating Influence in Vivo Circulation and Tumor Targeting of Hyaluronan-Grafted Liposomes |
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| المؤلفون: | Amer Alali, Hussaini Syed Sha Qhattal, Tanvirul Hye, Xinli Liu |
| المصدر: | ACS Nano |
| بيانات النشر: | American Chemical Society (ACS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Biodistribution, hyaluronan liposomes, Materials science, Light, Surface Properties, Mice, Nude, General Physics and Astronomy, Ligands, Endocytosis, Article, active tumor targeting, passive tumor targeting, Polyethylene Glycols, Mice, chemistry.chemical_compound, Phagocytosis, In vivo, Cell Line, Tumor, Neoplasms, PEG coating, PEG ratio, Hyaluronic acid, Animals, Humans, Scattering, Radiation, General Materials Science, CD44, Hyaluronic Acid, Liposome, General Engineering, accelerated clearance, Flow Cytometry, Ligand (biochemistry), Lipids, Molecular biology, In vitro, Hyaluronan Receptors, Nanomedicine, chemistry, Area Under Curve, Liposomes, HA polymer length, Female, Neoplasm Transplantation |
| الوصف: | Hyaluronan-grafted liposomes (HA-liposomes) preferentially target CD44-overexpressing tumor cells in vitro via receptor-mediated endocytosis. We investigated the pharmacokinetics and biodistribution of HA-liposomes with various sizes of HA (MW 5-8, 50-60, and 175-350 kDa) in mice. Incorporation of negatively charged HA on the liposome surface compromised its blood circulation time, which led to decreased tumor accumulation in CD44+ human breast cancer MDA-MB-231 xenografts compared to PEGylated liposomes (PEG-5000). Clearance of HA-liposomes was HA polymer length-dependent; high MW (175-350 kDa, highest ligand binding affinity) HA-liposomes displayed faster clearance compared to low MW (5-8, 50-60 kDa) HA-liposomes or PEGylated liposomes. Surface HA ligand density can also affect clearance of HA-liposomes. Thus, HA is not an effective stealth coating material. When dual coating of PEG and HA was used, the PEG-HA-liposomes displayed similar blood circulation time and tumor accumulation to that of the PEGylated liposomes; however, the PEG-HA-liposomes displayed better cellular internalization capability in vivo. Tumor histology showed that PEG-HA-liposomes had a more direct association with CD44+ cancer cells, while PEGylated liposomes located predominantly in the tumor periphery, with less association with CD44+ cells. Flow cytometry analysis of ex vivo tumor cells showed that PEG-HA-liposomes had significantly higher tumor cell internalization compared to PEGylated liposomes. This study demonstrates that a long blood circulation time is critical for active tumor targeting. Furthermore, the use of the tumor-targeting ligand HA does not increase total tumor accumulation of actively targeted liposomes in solid tumors; however, it can enhance intracellular delivery. |
| تدمد: | 1936-086X 1936-0851 |
| DOI: | 10.1021/nn405839n |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2ee866deacef028b1b1d8d8d810fa5ca https://doi.org/10.1021/nn405839n |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2ee866deacef028b1b1d8d8d810fa5ca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1936086X 19360851 |
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| DOI: | 10.1021/nn405839n |