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Polymer carriers for nuclear medicine
 Sedláček, Ondřej
In the thesis, we developed and studied a novel polymer delivery system for the DNA-intercalator bearing radioisotope iodine-125. Auger electrons emitting radioisotopes (such as iodine-125 or indium-111) are a potentially effective cancer treatment. Their use as an effective cancer therapy requires that they will be transported within close proximity of DNA, where they induce double-strand breaks leading to the cell death. This type of therapy may be even more beneficial when associated with drug delivery systems. The DNA intercalators proved to be effective carriers for the delivery of Auger electron emitters into DNA. Therefore, the new radioiodinated DNA-intercalating ellipticinium derivatives were synthesized and characterized. These compounds were linked to N-(2-hydroxypropyl) methacrylamide copolymer with narrow molecular weight distribution via acid-sensitive hydrazone linker. The structure of the linker plays a crucial role in the biological effectivity of the delivery system, so it was optimized to be stable at pH 7.4 (representing the pH of blood plasma), whereas in slightly acidic pH in endosomes after the cell internalization, the radioiodine-containing biologically active intercalator is rapidly released from its polymer carrier. The intercalating ability of the active compound was...
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