The formation of supramolecular bottle-brush polymers consisting of a non covalent backbone assembled through directional hydrogen bonds and of poly(isobutylene) (PIB) side-chains was investigated in cyclohexane by light scattering. Two limiting cases were observed depending on the balance between the favorable formation of hydrogen bonds and the unfavorable stretching of the PIB chains within the supramolecular bottle-brushes, in agreement with a theoretical model developed by Wang et al. On one hand, a bisurea self-assembling unit able to form four cooperative

Functional drug carrier systems have potential for increasing solubility and potency of drugs while reducing side effects. Complex polymeric materials, particularly anisotropic structures, are especially attractive due to their long circulation times. Here, we have conjugated cyclic peptides to the biocompatible polymer poly(2-hydroxypropyl methacrylamide) (pHPMA). The resulting conjugates were functionalized with organoiridium anticancer complexes. Small angle neutron scattering and static light scattering confirmed their self-assembly and elongated cylindrical shape. Drug-loaded nanotubes exhibited more potent antiproliferative activity toward human cancer cells than either free drug or the drug-loaded polymers, while the nanotubes themselves were nontoxic. Cellular accumulation studies revealed that the increased potency of the conjugate appears to be related to a more efficient mode of action rather than a higher cellular accumulation of iridium.

Self-assembling cyclic peptides (CP) consisting of amino acids with alternating d- and l-chirality form nanotubes by hydrogen bonding, hydrophobic interactions, and π-π stacking in solution. These highly dynamic materials are emerging as promising supramolecular systems for a wide range of biomedical applications. Herein, we discuss how varying the polymer conformation (linear vs. brush), as well as the number of polymer arms per peptide unimer affects the self-assembly of PEGylated cyclic peptides in different solvents, using small angle neutron scattering. Using the derived information, strong correlations were drawn between the size of the aggregates, solvent polarity, and its ability to compete for hydrogen bonding interactions between the peptide unimers. Using these data, it could be possible to engineer cyclic peptide nanotubes of a controlled length.

Size and shape have progressively appeared as some of the key factors influencing the properties of nanosized drug delivery systems. In particular, elongated materials are thought to interact differently with cells and therefore may allow alterations of in vivo fate without changes in chemical composition. A challenge, however, remains the creation of stable self-assembled materials with anisotropic shape for delivery applications that still feature the ability to disassemble, avoiding organ accumulation and facilitating clearance from the system. In this context, we report on cyclic peptide-polymer conjugates that self-assemble into supramolecular nanotubes, as confirmed by SANS and SLS. Their behaviour ex and in vivo was studied: the nanostructures are non-toxic up to a concentration of 0.5 g L and cell uptake studies revealed that the pathway of entry was energy-dependent. Pharmacokinetic studies following intravenous injection of the peptide-polymer conjugates and a control polymer to rats showed that the larger size of the nanotubes formed by the conjugates reduced renal clearance and elongated systemic circulation. Importantly, the ability to slowly disassemble into small units allowed effective clearance of the conjugates and reduced organ accumulation, making these materials interesting candidates in the search for effective drug carriers.

Cyclic peptide nanotubes were coupled to poly(oxazoline)s using a cleavable connection. Upon stimuli responsive detachment of the polymer an on-demand membrane activity could be achieved.

Polymers conjugated to cyclic peptides capable of forming strong hydrogen bonds can self-assemble into supramolecular bottlebrushes even in aqueous solutions. However, controlling the aggregation of these supramolecular assemblies remains an obstacle that is yet to be overcome. By introducing pH-responsive poly(dimethylamino ethyl methacrylate) (pDMAEMA) arms, the repulsive forces were tuned by adjusting the degree of protonation on the polymer arms.Neutron scattering experiments demonstrated that conjugates in an uncharged state will self-assemble into supramolecular bottlebrushes. Reducing the pH in the system led to a decrease in the number of aggregation, which was reversible by addition of base. Potentiometric titration showed a correlation between the number of aggregation and the degree of ionization of the pDMAEMA arms. Hence, a balance between the strength of the hydrogen bonds and the repulsive electrostatic interactions determines the number of aggregation and extent of self-assembly. The presented work demonstrates that conjugate selfassociation can be controlled by tuning the charge density on the conjugated polymer arms, paving the way for the use of responsive cyclic peptide conjugates in pharmaceutical applications.

The properties and structures of viruses are directly related to the three-dimensional structure of their capsid proteins,w hich arises from ac ombination of hydrophobic and supramolecular interactions,such as hydrogen bonds.The design of synthetic materials demonstrating similar synergistic interactions still remains ac hallenge.H erein, we report the synthesis of ap olymer/cyclic peptide conjugate that combines the capability to form supramolecular nanotubes via hydrogen bonds with the properties of an amphiphilic blockcopolymer. The analysis of aqueous solutions by scattering and imaging techniques revealed ab arrel-shaped alignment of single peptide nanotubes into al arge tubisome (length:2 60 nm (from SANS)) with ahydrophobic core (diameter:16nm) and ahydrophilic shell. These systems,which have astructure that is similar to those of viruses,w ere tested in vitro to elucidate their activity on cells.Remarkably,the rigid tubisomes are able to perforate the lysosomal membrane in cells and release asmall molecule into the cytosol.

The assembly of polymer building blocks into supramolecular bottlebrushes by non-covalent forces represents an exciting new field of research. This review provides an overview on suitable motifs and requirements for the formation of such structures.