Nanosized drug delivery systems (nanoDDS) posses the enormous potential to adjust pharmacokinetics of drugs, combine active agents and deliver them simultaneously or sequentially to finally improve therapeutic or diagnostic tools. Therefore, the material used for the nanoDDS needs be biocompatible, non-immunogenic and excretable or degradable within the body after performing the desired action.[1] In addition, the nanoDDS itself should be as simple as possible for the desired task to enable clinical translation. With respect to those needs we have developed different classes of nanoDDS, e.g. PeptoMicelles, PeptoNanoGels and PeptoPlexes, based on polypept(o)ides.[2] These block copolymers combine the polypeptoid polysarcosine (N-methylated glycine) and a polypeptide and are thus completely based on endogenous amino acids.While polysarcosine is used as a hydrophilic block ensuring “stealth-like” properties, proteinogenic amino acids, e.g. lysine, glutamic acid and cysteine, provide the desired chemical functionalities. The secondary structure of polypeptides can be used to direct the self-assembly process while core cross-linking introduces stability and functionality to the systems.[3] Disulfide bond formation has been used for core cross-linking and is introduced in one thiol-selective reaction using a novel class of reactive protective groups for cysteine [4], which yields long circulation nanoDDS (T1/2&gt;24h). This chemically clean, simple but very versatile synthetic pathway enables the synthesis of core cross-linked PeptoMicelles (hydrophobic core) or NanoPeptoGels (hydrophilic core) with adjustable morphology and core-functionality from the same block copolymer precursor. We present first applications of PeptoNanoGels (RNAi), PeptoPlexes (gene therapy) and PeptoMicelles (drug delivery and imaging). [1] M. Barz, R. Luxenhofer, R. Zentel, M.J. Vicent. Polymer Chemistry 2011, 2, 1900. [2] K. Klinker, M. Barz. Macromol. Rapid Commun. 2015, DOI: 10.1002/marc.201500403. [3] M. Talelli, M. Barz et al. Nano Today 2015, 10 (1), 93-117. [4] M. Barz et al. Thiol-Protected Amino Acids And Uses Thereof. EP14167291.5

Multifunctional polypept(o)ides: Adjusting particle morphology and function to biomedical applications

251st National Meeting (2016)

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