文摘
A polymer drug-carrier was synthesized by combining a monodisperse, sequence-defined poly(amidoamine) segment with a poly(ethylene oxide)-block (PAA-block-PEO). Between both polymer blocks asingle disulfide moiety is incorporated that allows for the realization of a programmed disassembly of the carrierpolymer in a reductive environment, like for instance present in certain intracellular compartments. The sequenceselective positioning is realized using cystamine as a new building block for the automated synthesis ofmonodisperse PAAs. The controlled disassembly of the polymeric carrier was used to establish a two-phaserelease process, e.g., highly relevant for an effective release after successful drug delivery into a cell. Theapplicability of this carrier was demonstrated by analyzing the complexation behavior of the system with plasmidDNA, before and after reductive degradation of the block copolymer. The presented observations describe atransition in polyplex (polymer-DNA complex) properties from PEO-stabilized ion complexes with soft chargecompensation to compact structures with more effective charge neutralization after cleavage of the PEO-block.