Specific antitumor targetable beta-cyclodextrin-poly(ethylene glycol)-folic acid drug delivery bioconjugate.

Abstract

The tumor targeting properties of a new drug carrier synthesized by bioconjugation of folic acid (FA) to beta-cyclodextrins through a poly(ethylene glycol) (PEG) spacer (CD-PEG-FA) were investigated. Surface plasmon resonance demonstrated that CD-PEG-FA specifically interacts with immobilized folate binding protein (FBP) while the naked beta-cyclodextrins do not display any specific interaction. In vitro studies demonstrated that CD-PEG-FA was devoid of cell toxicity. [(3)H]-folic acid/CD-PEG-FA competition binding investigations performed with folate receptor overexpressing human epidermal carcinoma KB cells showed that CD-PEG-FA had about 14 times lower tumor cell binding capacity than free folic acid. The carrier cell trafficking properties were investigated using rhodamine-B as fluorescent probe, which possesses 3000 and 4580 M(-)(1) inclusion constants for CD-PEG-FA and beta-cyclodextrins, respectively. Cell-associated fluorescence measurements showed that CD-PEG-FA does not promote the rhodamine-B uptake into non-folate receptor expressing human lung carcinoma MCF7 cells while 19% higher accumulation in KB cells was found with respect to rhodamine-B loaded beta-cyclodextrins. Confocal laser scanning microscopy indicated the presence of cytosolic red fluorescent spots after 2 h of incubation of KB cells with rhodamine-B included CD-PEG-FA. The fluorescent dye resided primarily in small spots, namely, endosomes and multivesicular bodies. At 1 h after pulsed incubation, wider red fluorescent cellular structures appeared as a fusion of previous structures.

• Authors: Stefano Salmaso, Alessandra Semenzato, Paolo Caliceti, Johan Hoebeke, Fabio Sonvico, Catherine Dubernet, Patrick Couvreur
• Journal: Bioconjugate chemistry (Bioconjug Chem) 2004 Sep-Oct Vol. 15 Issue 5 Pg. 997-1004 ISSN: 1043-1802 [Print] United States
• PMID: 15366952 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• beta-Cyclodextrins
• Polyethylene Glycols
• Folic Acid
• betadex

Topics

• Antineoplastic Agents (administration & dosage, analysis, chemistry)
• Cell Line, Tumor
• Drug Delivery Systems (methods)
• Folic Acid (administration & dosage, analysis, chemistry)
• Humans
• KB Cells
• Polyethylene Glycols (administration & dosage, analysis, chemistry)
• beta-Cyclodextrins (administration & dosage, analysis, chemistry)