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Nanopharmaceuticals or nanomedicines are defined as nanometer sized (1 to 1000 nm) complex systems, consisting of at least two components, one of which being the biologically active moiety such as a drug, peptide, protein or nucleotide. Several nano-sized hybrid therapeutics (e.g. polymer-protein conjugates) and drug delivery systems (liposomes and nanoparticles) have been approved for routine use in clinics. The term "polymer therapeutics" describes biologically active polymeric drugs, polymer-drug conjugates, polymer-protein conjugates, polymeric micelles to which a drug is covalently bound and multi-component polyplexes (containing covalent linkers) being developed as non-viral vectors for gene and protein delivery. Over the last decade, anticancer polymer therapeutics consisting of a drug covalently attached to a biocompatible polymeric carrier have been investigated intensively, and are currently in Phase I and II clinical trials. Polymers that have been most widely used to prepare these therapeutics are poly(N-(2-hydroxypropyl)methacrylamide), poly(ethylene glycol), polyglutamate and dextran, to which drug molecules (paclitaxel, campothecin or doxorubicin) are attached. These drugs are attached to the polymer backbone via a covalent linker that is stable in the circulation, but which releases the drug on arrival within the tumor cells. Linkers that have been used so far include peptides that are enzymatically cleaved by lysosomal enzymes as well as pH-sensitive cis-aconityl, hydrazone and acetal linkers that are hydrolyzed in the endosomal and lysosomal vesicles because of the local, acidic pH (4 - 6.5). Compared to low-molecular weight anticancer drugs, polymer therapeutics can offer a number of distinct advantages such as enhanced drug solubility and stability, increased plasma half-life as well as possibilities for passive targeting based on the enhanced permeability and retention (EPR) effect, which is based on the tendency of macromolecules of sufficient high molecular weight larger than 40 kDa to preferentially accumulate in tumor tissue. Keeping in mind the increasing clinical demand for innovative therapeutics, the aim of this Thesis was to prepare novel polymer therapeutics containing (more) effective non-covalent linkers to promote intracellular delivery of a bioactive cargo. In our conceptually novel design of polymer therapeutics, the bioactive cargo is attached to a polymer backbone via a non-covalent, biologically-inspired coiled coil linker, which is formed by heterodimerization of two complementary peptide sequences that are linked to the polymer carrier, respectively, the cargo. This new class of polymer therapeutics was designed to have similar properties and to follow the same endocytic cell uptake pathway as their covalent analogues. Delivery of the therapeutic cargo proceeds through a drop in pH in the endosomal compartments, which would disrupt the coiled coil complex. The motivation for using a heterodimeric coiled-coil linker lies in the possibilities to precisely manipulate peptide folding/unfolding by rational engineering of peptide primary structure. Additionally, the coiled coil linkers may play an active role in enhancing and directing intracellular transport and trafficking, for example by hybridization with target membrane proteins in cells, which could help the cytosolic or nuclear access of drugs. Finally, the proposed non-covalent polymer-drug conjugate provides a more universal strategy to conjugate a polymer carrier and a drug by facile "mix and match" approach and facilitates the creation of diverse polymer-drug libraries that are useful for a rapid screening of many materials parameters on the pharmaceutical properties of the conjugates. This Thesis consists of five chapters. Recent examples of non-natural, de novo coiled coil based bio(hybrid) materials that have been prepared are reviewed in Chapter 1. Chapter 2 will highlight the de novo E3/K3 heterodimeric coiled coil motif as an attractive candidate for the synthesis of stimuli responsive peptide-polymer conjugates for biomedical applications. The 24 amino acid long E3/K3 coiled coil motif is selected as it is stable at pH 7 but unfolds at pH 5, i.e. under conditions similar to those found in endosomal compartments. Chapter 3 describes the copolymerization behavior of N-(2-hydroxypropyl)methacrylamide (HPMA) with a coiled coil peptide derivative that is modified at the N-terminus with a methacryl moiety (K3-MA) in FRP and RAFT and explores the possibility for the synthesis of uniform, multivalent peptide-HPMA carriers. In Chapter 4, the design, synthesis and results of first in vitro model studies of a conceptually novel class of polymer therapeutics in which the cargo is attached to a polymer backbone via the E3/K3 coiled coil linker are presented. The aim of this proof-of concept study was to show that the E3/K3 coiled coil linker can be successfully used to bind the guest molecules to the PHPMA backbone during cell uptake and to release the guests intracellularly upon unfolding of the non-covalent E3/K3 linker. Chapter 5 deals with the cell uptake and trafficking properties of a series of non-covalent polymer-anticancer drug conjugates obtained by mixing a PHPMA carrier functionalized with multiple copies of K3 peptides with an equimolar amount of the anticancer drug methotrexate that is modified with the complementary peptide sequence (E3-MTX). Cytotoxicity and FACS experiments, which were carried out with anticancer drugs or fluorophore conjugates, provide insight into the cell uptake and trafficking behaviour of these conjugates.