Paclitaxel-clusters coated with hyaluronan as selective tumor-targeted nanovectors.
Paclitaxel (PTX) is a widely used anti-tumor agent in the treatment of solid tumors. Lack of selective strategies to target PTX into tumor cells together with poor solubility necessitating detergent, are severe clinical limitations. To address these hurdles, we devised a strategy that utilized PTX insolubility, mixing it with lipids that self-assemble into nanoparticle-like clusters. These clusters were then coated with hyaluronan, a glycosaminoglycan (GAG), and termed PTX-GAGs. These particles, delivered PTX selectively into tumor cells in a CD44-dependent manner. Injected systemically to mice bearing solid tumors, the PTX-GAGs showed high safety profile and tumor accumulation. Tumor progression was exponential upon treatment with free PTX or PTX in albumin nanoparticles (the FDA-approved Taxol and Abraxane, respectively). Under the same conditions, PTX-GAGs induced tumor arrest and were as potent as a 4-fold higher Taxol dose. Our findings suggest GAGs merit further investigation as vehicles for taxanes, and may be applicable as carriers in other therapeutic settings.
Rivkin
Ilia
I
Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Cohen
Keren
K
Koffler
Jacob
J
Melikhov
Dina
D
Peer
Dan
D
Margalit
Rimona
R
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016503:Drug Delivery Systems; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D017239:Paclitaxel / Q000737:chemistry* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D016207:Cytokines; D006820:Hyaluronic Acid; D017239:Paclitaxel