Interaction and transport of poly(L-lysine) dendrigrafts through liposomal and cellular membranes: the role of generation and surface functionalization.
Two generations of poly(l-lysine) dendrigrafts (DGLs) were studied with regard to their ability to interact with and translocate through liposomal and cellular membranes. Partial guanidinylation of the surface amino groups of the starting dendrigrafts afforded the guanidinylated derivatives whose membrane translocation properties were also assessed. Mixed liposomes, consisting of dihexadecyl phosphate, phosphatidylcholine, and cholesterol, were employed as model membranes, while A549 human lung carcinoma cells were used for cellular uptake studies. At high surface group/liposomal phosphate molar ratios and depending on the structure of the DGL, the interaction led to aggregation. Dendrigraft liposomal internalization was achieved, however, at low molar ratios. Thus translocation of the second generation dendrigrafts was rather limited at 25 degrees C, which, however, was enhanced when the bilayer was in the liquid-crystalline phase. In contrast, third-generation counterparts exhibited minor translocational ability. Furthermore, the introduction of a guanidinium group to dendrigrafts was found to enhance their transport through liposomal membranes. On the other hand, cellular uptake by A549 cells was monitored up to 3 h incubation time via fluorescence registration employing fluorescein-labeled dendrigrafts. The efficiency of dendrigraft internalization was enhanced by the presence of the guanidinium groups, while DGLs were preferentially localized in the nucleus and nuclear membrane, as revealed by fluorescence microscopy.
Tsogas
Ioannis
I
Institute of Physical Chemistry, NCSR Demokritos, 15310 Aghia Paraskevi, Attiki, Greece.
Theodossiou
Theodossis
T
Sideratou
Zili
Z
Paleos
Constantinos M
CM
Collet
Hélène
H
Rossi
Jean Christophe
JC
Romestand
Bernard
B
Commeyras
Auguste
A
D001672:Biocompatible Materials / Q000737:chemistry*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002784:Cholesterol / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D019791:Guanidine / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D008968:Molecular Conformation; D009685:Nuclear Envelope / Q000378:metabolism; D011107:Polylysine / Q000737:chemistry*; D021381:Protein Transport; D013499:Surface Properties
D001672:Biocompatible Materials; D008081:Liposomes; D011107:Polylysine; D002784:Cholesterol; D019791:Guanidine