Subcellular distribution of a new fluorinated, biocompatible, non-ionic telomeric carrier: a study in cultured B16 melanoma and rat skin fibroblasts.
Tris-hydroxymethyl-amino-methane telomers bearing a fluorinated end have recently been proposed as potential drug carriers. Using ion microscopy, we have investigated the cell uptake and subcellular distribution of a perfluorinated telomere, called F-TAC, in two cell lines, malignant murine B16 melanoma and normal rat skin fibroblasts. Single layer cell cultures on gold plates were incubated with F-TAC at different concentrations. Ion microscopy using mass spectrometry enabled the detection of Fluorine 19 atoms entering into F-TAC constitution. This microanalytical study showed an elective cytoplasmic localization of the molecule, wherein the distribution is relatively homogeneous. Within same culture and incubation conditions, intercellular variations in F-TAC content were very low. In the malignant line, the intracellular concentration remains practically identical when increasing F-TAC concentration in the culture medium above 0.2 mg/ml, indicating that the uptake phenomenon is saturable. In conclusion, the F-TAC telomer easily crosses the plasma membrane, however, it has difficulties in crossing the nuclear membrane. It is likely that intracellular penetration is essentially due to rapid endocytosis of the telomer.
Chehade
F
F
S.C.27 de 1'INSERM, Faculté de Médecine, Créteil, France.
Maurizis
J C
JC
Pucci
B
B
Pavia
A A
AA
Ollier
M
M
Veyre
A
A
Escaig
F
F
Jeanguillaume
C
C
Dennebouy
R
R
Slodzian
G
G
Hindié
E
E
D000818:Animals; D001692:Biological Transport; D002451:Cell Compartmentation; D004337:Drug Carriers; D005347:Fibroblasts; D006845:Hydrocarbons, Fluorinated / Q000302:isolation & purification* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure*; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*
D004337:Drug Carriers; D006845:Hydrocarbons, Fluorinated; C090337:fluorinated trisacryl conjugate