Endocytosis adsorptive

Plasmid DNA can be complexed electrostatically with cationic polymers. These complexes can be used for gene transfer [241]. Like the complexes of DNA with cationic lipids these complexes adhere to the cell surface with their cationic surface charges. Thereafter, they are internalized, presumably by adsorptive endocytosis. 

Marsh M, Helenius A. Adsorptive endocytosis of Semliki Forest virus. J Mol Biol 1980 142(3) 439 54. 

The cellular uptake of AS-ODN is an energy-dependent process and takes place in a saturable and sequence-independent manner [120,121]. The exact mechanism of uptake remains controversial. From in vitro experiments, some authors have proposed that the uptake is endocytic and mediated by membrane receptor proteins. The receptor responsible for the cellular uptake of AS-ODNs was reported to consist of both a 30-kDa protein [122] and an 80-kDa membrane protein [121]. However, other workers have argued that AS-ODN binding to membrane proteins is relatively non-specific and is mostly charge associated, consistent with adsorptive endocytosis or fluid-phase pinocytosis [101]. As a result of these conflicting reports, it is unlikely that in vitro data can be safely extrapolated to what occurs in the intact organism. 

Endocytosis involves the ceUular uptake of exogenous molecules or complexes inside plasma membrane-derived vesicles. This process can be divided into two major categories (1) adsorptive or phagocytic uptake of particles that have been bound to the membrane surface and (2) fluid or pinocytotic uptake, in which the particle enters the cell as part of the fluid phase. The solute within the vesicle is released intracellularly, possibly through lysosomal digestion of the vesicle membrane or by intermembrane fusion (Fig. 3.4). 

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...

FIGURE 14.1 Scheme of the proposed interaction mechanisms of liposomes with cells (a) adsorption, (b) endocytosis, (c) lipid exchange, and (d) fusion. (From Ostro, M. J. (1S8J.)Am. 257, 102-111. With permission.)... 

Cationic polymer is also frequently examined to increase the potential of a gene drug. Large molecular weight cationic polymers can condense pDNA more efficiently than cationic liposomes. They include poly-L-lysine (PLL), poly-L-omithine, polyethyleneimine (PEI), chitosan, starburst dendrimer and various novel synthetic polymers. These polymers can enhance the cellular uptake of pDNA by nonspecific adsorptive endocytosis. 

A (approximately 13.6 kDa) increases passage across the BBB by almost ninefold. Of the three fatty acid derivatives analyzed (myristic, palmitic, and stearic), the stearic modification had the greatest effect. The most likely mechanism for the entry of fatty acylated polypeptides to the brain is adsorptive endocytosis. 

Banks, W.A., V. Akerstrom, and A.J. Kastin. 1998. Adsorptive endocytosis mediates the passage of HIV-1 across the blood-brain barrier Evidence for a post-internalization coreceptor. J Cell Sci 111 (Pt 4) 533. 

Physical barrier. Following oral administration of macromolecular drugs, their potential absorption pathways from the intestinal lumen to the bloodstream can be classified into transcellular transport associated with adsorptive or receptor-mediated endocytosis and paracellu-lar transport (Fig. 10.1). The GI tract surface consists of a tightly bound single layer of epithelial cells covered with thick and viscous mucus, which serves as a defensive deterrent against permeation of xenobi-otics and harmful pathogens. The epithelial cells in the GI tract are... 

Figure 10.1 Pathways for intestinal absorption of macromolecular drugs, (a) Paracellular transport of macromolecules can be achieved by altering or disrupting the tight junctions that exist between cells and are only permeable to small molecules (<100 to 200 Da). (b) Adsorptive enterocytes and (c) M cells of Peyer s patches allow transcellular transport of macromolecules involving transcytosis and receptor-mediated endocytosis.

Cellular internalization of macromolecules by endocytosis is an important biological process for their transcellular transport. Endocytosis can be categorized into adsorptive and receptor-mediated endocytosis (RME). RME involves specific binding of ligand to the receptor on the apical cell... 

Raub TJ, Audus KL. Adsorptive endocytosis and membrane recycling by cultured primary bovine brain microvessel endothelial cell monolayers. J Cell Sci 1990 97 (pt 1) 127—138. 

Gene delivery systems can distribute plasmids to the desired target cells, after which the plasmid is internalized into the cell by a number of mechanisms, such as adsorptive endocytosis, receptor-mediated endocytosis, micropinocytosis, caveolae-mediated endocytosis and phagocytosis (see Section 1.3.3.2). The intracellular fate of plasmids depends on the means by which they are internalized and translocated to the cytoplasms and then to the nucleus. In coated-pit endocytosis, DNA complexes first bind to the cell surface, then migrate to clathrin-coated pits about 150 ran in diameter and are internalized from the plasma membrane to form coated vesicles. 

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