Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells.
Glioblastoma Multiforme (GBM) is a highly prevalent and deadly brain malignancy characterized by poor prognosis and restricted disease management potential. Despite the success of nanocarrier systems to improve drug/gene therapy for cancer, active targeting specificity remains a major hurdle for GBM. Additionally, since the brain is a multi-cell type organ, there is a critical need to develop an approach to distinguish between GBM cells and healthy brain cells for safe and successful treatment. In this report, we have incorporated hyaluronic acid (HA) as an active targeting ligand for GBM. To do so, we employed HA conjugated liposomes (HALNPs) to study the uptake pathway in key cells in the brain including primary astrocytes, microglia, and human GBM cells. We observed that the HALNPs specifically target GBM cells over other brain cells due to higher expression of CD44 in tumor cells. Furthermore, CD44 driven HALNP uptake into GBM cells resulted in lysosomal evasion and increased efficacy of Doxorubicin, a model anti-neoplastic agent, while the astrocytes and microglia cells exhibited extensive HALNP-lysosome co-localization and decreased antineoplastic potency. In summary, novel CD44 targeted lipid based nanocarriers appear to be proficient in mediating site-specific delivery of drugs via CD44 receptors in GBM cells, with an improved therapeutic margin and safety.
Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.
Stephen L
SL
Hayward
Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.
Christina L
CL
Wilson
Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.|Nebraska Center for Materials and Nanoscience, Lincoln, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.|Nebraska Center for the Prevention of Obesity Diseases, University of Nebraska-Lincoln, NE, Lincoln, 68583, USA.|Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA.|Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha NE, 68198, USA.
Srivatsan
S
Kidambi
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D006820:Hyaluronic Acid; D008081:Liposomes; D051379:Mice; D053758:Nanoparticles; D051381:Rats
D000970:Antineoplastic Agents; D018960:Hyaluronan Receptors; D008081:Liposomes; D004317:Doxorubicin; D006820:Hyaluronic Acid
CD44 targeting; glioblastoma; hyaluronic acid; lipid nanoparticles; nanomedicine