Endocytosis mechanism

Oehlke and coworkers have described the cellular uptake properties of a simple a-hehcal amphipathic model peptide sequence (Lys-Leu-Ala-Leu-Lys-Leu-Ala-Leu-Lys-Ala-Leu-Lys-Ala-Ala-Leu-Lys-Leu-Ala) in the context of a drug delivery vehicle [72]. On the basis of the data presented, it was proposed that non-endocytosis mechanism(s) were involved in the uptake into mammalian cells. The similarity between our b2 aPNA-sequence to that of this amphipathic model peptide makes it tempting to suggest that a similar uptake mechanism is involved in the cellular uptake of aPNAs. Further experimentation is necessary to test this hypothesis. 

Regarding the mechanism of biomolecules functionalized CNTs entering into cells, endocytosis mechanism may be responsible for the phenomena, a theory model is also suggested (Gao et al., 2005) the optimal size of particles entering into cells is between 20 nm and 700 nm or so, too small nanopaiticles are very difficult to enter into cells because of cellular surface tension force and adhesion. The further mechanism of effects of CNTs on human healthcare and environment is being investigated from the following four scales such as molecular, cellular, animals, and environment levels. 

Weissleder et al. [84] first showed that the human transferrin receptor (hTfR) can be used to internalize MRI contrast agents. The hTfR regulates cellular uptake of iron from transferrin, a plasmatic iron transport protein [85], via a receptor mediated endocytosis mechanism. Thus, MION particles (dextran coated iron oxide) were oxidized with sodium periodate. Holotransferrin was added and the resulting Schiff base adduct was reduced with sodium cyanoborohydride to give transferrin labeled MIONs, Tf-MION (Scheme 3). 

How do calixarenes enter cells To answer this question Matthews, Mueller and co-workers prepared a soluble calix[4]arene with quaternary ammonium groups on the upper rim and a fluorescent label on the lower rim [35], Following the progress of the compound by fluorescence confocal microscopy it was apparent that molecules were not transported across the membrane by normal endocytosis mechanisms, nor did they penetrate the cell nucleus but remained in the cytoplasm. This would seem to point to a membrane bound channel as the point of entry and paves the way for an array of therapeutic interventions. 

Vives E. Cellular uptake of the Tat peptide An endocytosis mechanism following ionic interactions. J Mol Recognit 2003 16 265-71. 

Ox-LDL), and enzymatically modified LDL (E-LDL). They differ in their uptake/receptor-mediated recognition and endocytosis mechanisms and are delivered to lysosomes. In this review, especially E-LDL and Ox-LDL as two principal chemical modifications of LDL are described. 

A key question is whether the hormone acciunulated by the cells actually crosses the plasma membrane. In fibroblasts, this has been demonstrated directly by fluorescence microscopy showing that rhodamine-labeled T3, after attaching to the cell surface, moves into coated pits and then enters the cytoplasm via coated vesicles. This energy-dependent phenomenon can be blocked by endocytosis inhibitors such as monodansylca-daverine (MDC). We have shown that MDC also inhibits T3 and uptake by mouse neuroblastoma and htiman medulloblastoma and glioma cells. Some of these data are given in Fig 4. They indicate that thyroid hormone uptake by cells of the CNS probably involves a receptor-mediated endocytosis mechanism. 

Transferrin as a ligand efficiently transfers small MW drugs, liposomes, and macromolecules through a receptor-mediated endocytosis mechanism (Deshpande et al. 1994) because the transform receptors are found on many mammalian cells (Dautry-Varsat 1986). Mao et al. (2001) coupled transferrin with chitosan nanoparticles prepared by chitosan and sodium sulfate. The transferrin-conjugated chitosan nanoparticles showed a fourfold increase of transfection efficiency in HEK293 cells and HeLa cells as compared with the chitosan ones. 

Grafting different bioactive components onto hyaluronan improves the stability of the complex. With assistance of the CD44 receptors, such complexes have ability of prolonged transportation into cells missing key metabolites using the endocytosis mechanism. 

Kim et al. prepared maimosylated chitosan (MC) to obtain receptor-mediated endocytosis for targeting to APCs [39]. The results indicated that MC/DNA complexes showed higher transfection efficiency compared with WSC/DNA complexes in Raw 264.7 cells, owing to the receptor-mediated endocytosis mechanism [39]. They also performed interleukin 12 (lL-12) gene delivery through intratumoral injection of MC/IL-12 complexes into B ALB/C mice bearing tumors at the injected sites [40]. Intratumoral delivery of MC/EL-12 complexes suppressed more tumor growth than the control due to the mechanism of apoptosis and cell cycle arrest. 

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