Nanomedicines are expected to have major impact on the development of pharmaceuticals during the 21stcentury, because they bear the potential to adjust pharmacokinetics of drugs, combine different bioactive agents and deliver them simultaneously.To design nanoparticles and adjust material properties to the desired application a controlled synthesis of polymers is necessary to ensure polymer functionality and reproducibility.1 Thus, polymers derived from controlled polymerizations are required to fulfill these needs. In respect to a medical application, polymers need to fulfill further requirements, such as biocompatibility, non-immunogenicity and the ability to be excreted or even better metabolized within the body after performing the desired action.One remarkable polymeric material fulfilling these needs are polypeptides. One versatile pathway to protein mimics is the polymerization of a-aminoacid-N-carboxyanhydrides. Although this technique cannot provide sequence control it allowes to adjust chain length, architecture, functionality and immunogenic properties to a specific need and include functionalities beyond nature's possibilities.2We have developed various polypeptides based on natural amino acids having molecular weights from 10 � 40 kDa and dispersities around 1.1. While polysarcosine was used a hydrophilic block ensuring stealth-like properties derivatives of lysine, glutamic acid and cysteine carry reactive groups. These groups can be selectively addressed and create amphiphilic block copolypeptides and enable conjugation of bioactive agents or crosslinking of nanoaggregates. By adjusting polymer properties as well as conditions of aggregate formation we were able to synthesize PeptoNanoGels (siRNA and oligoDNA delivery), PeptoPlexes (pDNA delivery) and PeptoMicelles (drug delivery and imaging) in the size range of 40 to 200 nm.The systems have been applied to cancer immunotherapy, chemotherapy of solid tumors as well as controlled release systems for inhibitors for disease related enzymes. References 1) M. Barz et al. Polymer Chemistry, 2011 , 2, 1900-1918.2) M. Barz et al. Polym. Chem. 2013 , 4, 2989-2994.

Introducing peptomicelles, nanopeptogels and peptoplexes: A journey from synthesis of polypeptides to nanoparticles for immunotherapy and diagnostics

247th National Meeting (2014)

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