Receptor-targeted polymer vesicles

Fig. I. Endocytic pathways used by cells to internalize soluble macromolecules [25] fluid-phase pinocytosis (1), adsorptive pinocytosis (2), and receptor-mediated endocytosis (pinocytosis) (6). Each of these processes involves a formation of a sealed vesicle formed from the plasma membrane which encloses part of the extracellular medium. The internalization of a polymer-drug conjugate (P-D), and targeted polymer-drug conjugate ( => —P-D) is shown. Other abbreviations — = cell surface receptor/antigen 1 = clathrin molecule X = lysosomal enzyme. Fluid-phase pinocytosis (1) and adsorptive pinocytosis (2) are nonspecific processes which direct the macromolecule into the lysosomal compartment of the cell. Once P-D is internalized, whether by (1) or (2), the resulting endosome (3) is ultimately fused with a primary lysosome (4) forming a secondary lysosome (5). In the latter compartment P-D is in contact with several types of lysosomal enzymes. The membrane of (5) is impermeable to macromolecules. Consequently, the structure of P-D may be designed in such...

To bring the nanocontainer to a specific place where it should release its pay-load, targeting is a required approach. Hence, much work has been carried out to attach ligands or antibodies to the hydroxyl end-group of PEG-based assemblies [150,181,243], Biotinylated nondegradable block copolymer assemblies have been shown to attach to surfaces coated with the biotin receptor avidin [146,147, 150,244], Coupling chemistry has been applied to conjugate either an antihuman IgG, or antihuman serum to PEG-carbonate- or PEG-polyester-assembled polymer vesicles [149,245], HIV-derived Tat peptide attached to PEG-PBD polymersomes enhanced the cellular delivery of nanoparticles [246] and increased dendritic cell uptake in vitro [181]. 

Figure 6.5 (A) Schematic representation of a pol mier-lipid hybrid vesicle, surface functionalized with HER2/neu receptor. (B) Polymer-lipid vesicles from PEO-PBD/HSPC blends show significantiy enhanced tumor targeting activity compared to the block copol mier alone.

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