The enormous potential of polymeric nanomedicines arises from the possibility to combine desirable material properties with compartmentalized functionalities in one distinct nanoparticle. The price to pay for this multi-functionality is the intrinsic complexity of these systems. Synthetic complexity is a major drawback for clinical translation and can prevent even the most effective nanomedicines from becoming drugs, since it complicates up-scaling and can affect reproducibility of material properties. Therefore, a major task for polymer chemists is the development of synthetic pathways, which intrinsically reduces chemical complexity, while preserving the desired functionality. With respect to these needs, we have developed reactive polypept(o)ides (polypeptoid-block-polypeptide copolymers), which can be synthesized with precise control over molecular weight, low polymer dispersity and high end group integrity. Furthermore, this class of materials is completely based on endogenous amino acids and combines the stealth-like properties of polysarcosine with the multi-functionality of polypeptides. Novel S-alkylsulfonyl-l-cysteines are stable against hard nucleophiles enabling the controlled synthesis of reactive homopolymers and amphiphilic block copolypept(o)ides, but are highly reactive against thiols (soft nucleophiles) forming disulfide bonds. Thus, they are currently the only reactive amino acid derivative that can be synthesized and directly applied to chemoselective disulfide formation (full conversion in less than 1 min, no side products). Disulfide bond formation is particularly attractive for the stabilization of polymer aggregates, since sulfur-sulfur bonds are stable in extra-cellular environments (blood stream) but readily cleaved inside cells. In addition, the hydrophobic nature of poly(S-alkylsulfonyl-l-cysteines) and their tendency to form β-sheets enables secondary structure controlled self-assembly in aqueous solution. This toolbox enables the straightforward synthesis of core cross-linked micelles (PeptoMicelles) and nanohydrogels (PeptoNanoGels) with control over morphology and core polarity. Besides secondary structure-controlled self-assembly, bottlebrush polymers (PeptoBrushes) and star-like polymers (PeptoStars) are accessible by bottom up synthesis by employing multivalent initiators. An overview on the application of polypept(o)ide based nanoparticles in therapy and diagnosis will be presented.

Polypept(o)ides: Combining polypeptoids with polypeptides for diagnosis and therapy

254th National Meeting (2017)

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