The tumour targeting properties of a new drug carrier synthesised by bioconjugation of folic acid to beta-cyclodextrins through a PEG spacer (CD-PEG-FA) were investigated. Surface plasmon resonance demonstrated that CD-PEG-FA interacts specifically with immobilized folate binding protein (FBP) with apparent dissociation constant of 3.59 nM while the naked beta-cyclodextrins did not display any specific interaction. Cell culture studies showed that CD-PEG-FA was devoid of cell toxicity. [3H] folic acid/CD-PEG-FA competition binding investigations performed with over-expressing folate receptor human epidermal carcinoma KB cells showed that CD-PEG-FA had about 10 times lower tumour cell binding capacity than folic acid free. The carrier cell trafficking properties were investigated using rhodamine-B as fluorescent probe, which possesses 3000 M-1 and 4600 M-1 inclusion constants for CD-PEG-FA and beta-cyclodextrins, respectively. Cell associated fluorescence measurements showed that CD-PEG-FA did 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 native beta-cyclodextrins. Confocal laser scanning microscopy evidenced the presence of cytosolic red fluorescent spots after 2 hours incubation of KB cells with rhodamine-B CD-PEG-FA inclusion. The fluorescent dye resided primarily into small spots, namely endosomes and multi-vescicular bodies. At 1 hour after pulsed incubation wider red fluorescent cellular structures appeared as fusion of previous structures.

Specific antitumor targetable beta-cyclodextrin-poly(ethylene glycol)-folic acid drug delivery bioconjugate / Salmaso, S.; Semenzato, A.; Caliceti, P.; Hoebecke, J.; Sonvico, Fabio; Dubernet, C.; Couvreur, P.. - In: BIOCONJUGATE CHEMISTRY. - ISSN 1043-1802. - 15:5(2004), pp. 997-1004. [10.1021/bc034186d]

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

SONVICO, Fabio;
2004-01-01

Abstract

The tumour targeting properties of a new drug carrier synthesised by bioconjugation of folic acid to beta-cyclodextrins through a PEG spacer (CD-PEG-FA) were investigated. Surface plasmon resonance demonstrated that CD-PEG-FA interacts specifically with immobilized folate binding protein (FBP) with apparent dissociation constant of 3.59 nM while the naked beta-cyclodextrins did not display any specific interaction. Cell culture studies showed that CD-PEG-FA was devoid of cell toxicity. [3H] folic acid/CD-PEG-FA competition binding investigations performed with over-expressing folate receptor human epidermal carcinoma KB cells showed that CD-PEG-FA had about 10 times lower tumour cell binding capacity than folic acid free. The carrier cell trafficking properties were investigated using rhodamine-B as fluorescent probe, which possesses 3000 M-1 and 4600 M-1 inclusion constants for CD-PEG-FA and beta-cyclodextrins, respectively. Cell associated fluorescence measurements showed that CD-PEG-FA did 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 native beta-cyclodextrins. Confocal laser scanning microscopy evidenced the presence of cytosolic red fluorescent spots after 2 hours incubation of KB cells with rhodamine-B CD-PEG-FA inclusion. The fluorescent dye resided primarily into small spots, namely endosomes and multi-vescicular bodies. At 1 hour after pulsed incubation wider red fluorescent cellular structures appeared as fusion of previous structures.
2004
Specific antitumor targetable beta-cyclodextrin-poly(ethylene glycol)-folic acid drug delivery bioconjugate / Salmaso, S.; Semenzato, A.; Caliceti, P.; Hoebecke, J.; Sonvico, Fabio; Dubernet, C.; Couvreur, P.. - In: BIOCONJUGATE CHEMISTRY. - ISSN 1043-1802. - 15:5(2004), pp. 997-1004. [10.1021/bc034186d]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1722107
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