Interaction Of Capsules And Living Cells

Cells can incorporate objects ranging from the molecular up to the micrometer scale by processes including pino-, endo-, and phagocytosis. Surprisingly, uptake by living cells of several polyelectrolyte capsules as big as 5 μm has been demonstrated by different groups and to date it is a fact that capsules of different sizes, ranging from the nanometer to the micrometer size, are spontaneously ingested by a huge variety of cells. Currently, there are numerous studies concerning the cellular internalization mechanism of capsules. In most cases, phagosomal/endosomal/lysosomal perinuclear compartments were suggested as final locations of the capsules, similar to that which is claimed for colloidal nanoparticle. A lipid raft-mediated uptake mechanism based on the previous results by Rejman , who revealed size-dependent internalisation of ligand-devoid particles.

Although strictly speaking the detailed uptake process of polyelectrolyte capsules by cells remains to be clarified in future studies, some important parameters that regulate this process have recently been elucidated. For instance, the overall charge of capsules has been demonstrated to play a role for capsule uptake. As for smaller colloidal nanoparticles, charged capsules are ingested faster than uncharged ones, and positively charged capsules are found to be ingested more than negatively charged ones. At any rate, adsorption of cell medium proteins to the capsule surface tends to smear out differences in surface chemistry for long incubation times. Atomic force microscopy measurements of adhesive forces between capsules and cell membranes show that the uptake of polyelectrolyte capsules strongly correlates with the adhesion of capsules to the outer cell membrane. In addition, it is frequently observed that capsules are deformed upon the incorporation process due to the mechanical stress caused in the intracellular space. Deformation naturally depends on the structure of the capsule walls. Recently, heat-shrunken capsules that do not lose their cargo, even upon compression inside cells, have been demonstrated. The capsule uptake rate of cells can also be regulated by using the molecular recognition system of cells. By attaching specific ligands to the capsule surface (fig 5), the capsule uptake rate of target cells, which are expressing the corresponding receptors, can be increased. On the other hand, non-specific uptake of capsules by cells can be also reduced by immobilizing polyethylene glycol (PEG) on their surface.

Fig. 5. (a) Magnetic targeting of capsules for local accumulation. Capsules functionalized with magnetic NPs (black) are trapped in a magnetic field gradient created with a permanent magnet. Fluorescent NPs (green) in the capsule walls permit visualization by optical techniques. (b) Specific uptake of capsules by cells via molecular recognition. The surface of the capsules is functionalized with ligands that bind to corresponding receptors localized in the membrane of target cells.

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As ‘foreign objects’, capsules may well induce harmful effects on living cells. Toxicity can originate from two different sources, from the actual polyelectrolyte capsules and from the functional nanoparticles embedded in the capsule walls. Initial studies have suggested that capsules alone do not exhibit acute cytotoxic damage on cell cultures, but rather that the nanoparticles with which the capsules are functionalized are potentially cytotoxic, as for example when Cd-based semiconductor nanoparticles embedded in the capsule walls corrode and release toxic cadmium ions. On the other hand, both magnetic and gold nanoparticles are relatively harmless to the cells. Cytotoxicity assays in vitro have been employed to confirm the innocuousness of polyelectrolyte-based systems, although more advanced studies involving animal tissue also demonstrate that plain unfunctionalized capsules can cause local inflammations. Despite the impact this would have on medical applications, the cytotoxicity effects of capsules have not yet been fully investigated.