Combined atomic force microscopy and optical microscopy measurements as a method to investigate particle uptake by cells.

We propose a combination of atomic force microscopy (AFM) and optical microscopy for the investigation of particle uptake by cells. Positively and negatively charged polymer microcapsules were chosen as model particles, because their interaction with cells had already been investigated in detail. AFM measurements allowed the recording of adhesion forces on a single-molecule level. Due to the micrometer size of the capsules, the number of ingested capsules could be counted by optical microscopy. The combination of both methods allowed combined measurement of the adhesion forces and the uptake rate for the same model particle. As a demonstration of this system, the correlation between the adhesion of positively or negatively charged polymer microcapsules onto cell surfaces and the uptake of these microcapsules by cells has been investigated for several cell lines. As is to be expected, we find a correlation between both processes, which is in agreement with adsorption-dependent uptake of the polymer microcapsules by cells.

Nanoengineered polymer capsules: tools for detection, controlled delivery, and site-specific manipulation.

We present the concept of multifunctional nanoengineered polymer capsules and outline their applications as new drug delivery systems or supramolecular toolboxes containing, for example, enzymes capable of converting nontoxic prodrugs into toxic drugs at a designated location. Such functionalized nanocontainers offer a wide range of applications including enzymatic catalysis, controlled release, and directed drug delivery in medicine due to their multifunctionality. The unique advantage of capsules in comparison to other systems is that they can be functionalized or loaded simultaneously with the above-mentioned components, thus permitting multifunctional processes in single cells.

Magnetic targeting and cellular uptake of polymer microcapsules simultaneously functionalized with magnetic and luminescent nanocrystals.

By using a flow channel system for modeling the bloodstream in the circulatory system and by locally creating a magnetic field gradient caused by a permanent magnet, we demonstrate specific trapping of polymer capsules simultaneously functionalized with two types of nanoparticles--magnetic and luminescent nanocrystals. In the regions where the capsules were trapped by the magnetic field, drastically increased uptake of capsules by cells has been observed. The uptake of capsules by cells could be conveniently monitored with a fluorescence microscope by the luminescence of CdTe nanocrystals that had been embedded into the shells of the capsules. Our experiments envisage the feasibility of magnetic targeting of polymer capsules loaded by pharmaceutical agents to pathogenic parts of a tissue.