Folate-mediated targeting of albumin conjugates of paclitaxel obtained through a heterogeneous phase system.
The study developed cytotoxic macromolecular conjugates that specifically target the folate receptor and deliver the drug into cell cytoplasm. The anticancer agent paclitaxel was conjugated to human serum albumin (HSA) and this drug-albumin conjugate was further equipped with folic acid, linked via an extended poly(ethylene glycol) spacer. Preparation was carried out in a heterogeneous phase system exploiting the binding ability of Cibacron Blue dye to HSA. Unreacted reagents were easily removed and, after purification by gel filtration, the conjugate was fully characterized. Binding and in vitro cytotoxicity studies on human nasopharyngeal epidermal carcinoma KB and colorectal carcinoma HT-29 cells (as negative control) demonstrated increased selectivity and anti-tumoral activity.
Dosio
Franco
F
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, via Giuria 9, 10125 Torino, Italy. franco.dosio@unito.it
Arpicco
Silvia
S
Stella
Barbara
B
Brusa
Paola
P
Cattel
Luigi
L
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D015179:Colorectal Neoplasms / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014227:Triazines / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D012709:Serum Albumin; D014227:Triazines; D011092:Polyethylene Glycols; C012842:Cibacron Blue F 3GA; D005492:Folic Acid; D017239:Paclitaxel