Cellular internalisation

Determination of the exact mechanism leading to cellular internalisation of CNTs is considered very important in their development as components of biomedical devices and therapeutics intended for implantation or administration to patients. One of the most important parameters in all such studies is the type of nanotubes used, determined by the process by which they are made biocompatible. Interactions with cells have to be performed using biocompatible CNTs, achieved by either covalent or noncovalent surface functionalisation that results in water-dispersible CNTs. A variety of different functionalisation strategies for CNTs have been reported by different groups, therefore direct comparisons are often hampered by the inability to correlate experimental conditions. 

Fig. 2.2 Cellular internalisation pathways proposed for carbon nanotubes (CNTs) (A) phagocytosis (B) membrane piercing by passive diffusion (C) caveolae-mediated endocytosis and (D) clathrin-mediated endocytosis... 

Zava O, Mattsson J, Therrien B, Dyson PJ (2010) Evidence for drug release from a metalla-cage delivery vector following cellular internalisation. Chem Eur J 16 1428-1431... 

A detailed quantitative evaluation of tracer kinetics requires the use of compartment modelling. A two-tissue compartment model is used for the evaluation of the dynamic studies. This is a standard methodology in particular for the quantification of dynamic FDG studies (13-15). Concerning the 68Ga-peptide kinetics, again the two-tissue compartment model is applied to the data. In case of 68Ga-labelled peptides, DOTATOC or bombesin, kl is associated with the receptor binding, k2 with the displacement from the receptor, k3 with the cellular internalisation, and k4 with the externalisation. The fractional blood volume... 

Chemically stable analogues of acyclovir (26) have been synthesised in an attempt to attain appreciable activity against herpes virus type-1 while allowing their cellular internalisation and bypassing the intracellular activation of acyclovir to its triphosphate derivative required for activity. These compounds are bio-isosteres of acyclovir monophosphate and diphosphate, but are devoid of any appreciable antiviral activity on both HSV-1 and HIV-1. 

Polymersomes size is crucial for the design of drug delivery systems. Size governs the fate of particles both in vitro and in vivo. Cellular internalisation can drop by three orders of magnitude, going from 100 to 400 nm [70], In vivo the size determines the particles circulation times, their ability to reach specific target, the... 

For undersaturated ([M] < Km) systems with relatively fast internalisation kinetics (kmt > k, ), the uptake of trace metals may be limited by their adsorption. Because the transfer of metal across the biological membrane is often quite slow, adsorption limitation would be predicted to occur for strong surface ligands (small values of k ) with a corresponding value of Km (cf. equations (35) and (36)) that imposes an upper limit on the ambient concentration of the metal that can be present in order to avoid saturation of the surface ligands. More importantly, as pointed out by Hudson and Morel [7], this condition also imposes a lower limit on the carrier concentration. Since the complexation rate is proportional to the metal concentration and the total number of carriers, for very low ambient metal concentrations, a large number of carriers are required if cellular requirements are to be satisfied. 

Cellular Responses Affecting Trace Element Internalisation... 

There are two direct consequences of insulin binding to the receptor. First the tyrosine kinase activity on the / -subunit is activated. This causes autophosphorylation and also phosphorylation of intracellular proteins. Although a number of proteins have been phosphorylated in vitro, it is not yet clear what is the normal physiological substrate or substrates. In mammals, several cellular protein substrates have been proposed, but the precise role of any of the proteins is unclear. A 70 kDa protein has been proposed as a substrate in cultured foetal chick neurons, and a 72 kDa phosphoprotein in domestic fowl hepatoma, but the functions of these polypeptides are unclear (Simon Taouis, 1993). Second, binding causes internalisation of the receptor, after which the insulin is removed and degraded in the lysosomes and the receptor recycled back to the plasmalemma. In domestic fowl hepatocytes, the half-life of the receptor is about 10 h (Simon, 1989). 

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