(6) The current clinical standard for stealth polymers used in many drug formulations is poly(ethylene glycol) (PEG). The coupling of stealth polymers to polymeric drug carriers can prevent their recognition by the RES and thereby decreases unspecific side effects and also the necessary amount of polymer-encapsulated drug to be administered. (4) In the worst case, the RES additionally triggers an inflammatory response which decreases the effectiveness of further nanoparticle-based drug applications due to the generation of specific antibodies against these carriers. Since polymer-based nanoparticles are foreign bodies for the host, the reticuloendothelial system (RES) recognizes, engulfs, and destroys them. The resulting short circulation time decreases the risk for nonspecific uptake and detrimental side effects. Their small size further leads to rapid renal filtration and elimination. (3) Their small size leads to favorable tissue penetration properties, which allows them to reach even poorly perfused tissue, e.g., hypoxic tumor areas. (2) Nanocarriers such as micelles below 50 nm in diameter were reported to be preferable in the use of tumor treatment. (1) For the encapsulation and the controlled release of numerous small molecules, polymeric drug carrier systems represent attractive vehicles for tissue-specific drug delivery. Often, carriers are used which employ active, passive, or a combination of both targeting strategies to enrich their payload in the desired environment. Targeting drugs to a desired tissue or cell-type is a common goal of modern pharmaceutical approaches. Whereas an efficient stealth effect was found for micelles formed from polymers with anionically charged or thiol end groups, a hydrophobic end group altered the micelles’ structure sufficiently to adapt cell-type specificity and stealth properties in the liver. Although various micelles appeared similar in dynamic light scattering and cryo-transmission electron microscopy, changes in the micelles were evident from principal component analysis of the Raman spectra. To understand these effects, the end group was additionally modified by the attachment of four methacrylic acid repeating units. Despite the high molar mass of the individual macromolecules ( M n ≈ 20 kg mol –1), backbone end group modification by attachment of a hydrophilic anionic fluorescent probe strongly affected the in vivo performance. Dye-loaded micelles of 10 nm diameter formed from amphiphilic graft copolymers composed of a hydrophobic poly(methyl methacrylate) backbone and hydrophilic poly(2-ethyl-2-oxazoline) side chains with a degree of polymerization of 15 were investigated concerning their cellular interaction and uptake in vitro as well as their interaction with local and circulating cells of the reticuloendothelial system in the liver by intravital microscopy.
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