Interaction and Transport of Poly(l-lysine) Dendrigrafts through Liposomal and Cellular Membranes:  The Role of Generation and Surface Functionalization

Abstract

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.

Targeted imaging of activated caspase-3 in the central nervous system by a dual functional nano-device

“…DGLs are thought to be degradable, consisted of lysine monomer and rich of primary amino-groups [21,22]. They were selected as initial vector of this nano-device because of rich amino groups which can be easily modified and high biocompatibility.…”

Arginine end-functionalized poly(l-lysine) dendrigrafts for the stabilization and controlled release of insulin

“…A series of partially guanidinylated poly(L-lysine) dendrigrafts of the second generation with 12, 24, 36 guanidinium groups and the fully functionalized dendrigraft with 48 guanidinium groups was prepared (Scheme 1) by a method analogous to one previously reported [40]. Thus, to 0.05 mmol poly(L-lysine) dendrigraft dissolved in dry DMF (20 mL), a DMF solution (10 mL) containing 0.…”

An Expeditious Multigram‐Scale Synthesis of Lysine Dendrigraft (DGL) Polymers by Aqueous N‐Carboxyanhydride Polycondensation

“…), as illustrated by, for example, a recent investigation on interactive transport properties of DGL (either native or chemically modified) through liposomal and cellular membranes. [39] Experimental Section Materials: N a -Carbamoyl,N e -trifluoroacetyl-l-lysine, C-LysA C H T U N G T R E N N U N G (Tfa), was prepared and purified according to Taillades et al [29] from N e -trifluoroacetyll-lysine LysA C H T U N G T R E N N U N G (Tfa), which was generously supplied by Degussa (purity 99 % by HPLC), and used without further purification. Acetonitrile (MeCN; Baeckeroot Labo, Jacou, France) was stored over 4 molecular sieves.…”