Front Cover: A new approach to prepare free‐standing biodegradable nanopillar arrays on flexible substrates is developed by using plasma etching with block copolymer micelles encapsulating Au nanoparticles as an etching mask. This method can offer a feasible route to create vertically‐aligned nanostructures of various materials with dimensional controllability. This is reported by Gyeong Won Lee, Seunghyun Lee, Jang Hwan Kim, Sang‐Gu Yim, Jooyeon Ryu, Eunji Lee, Jaebeom Lee, Seong Il Yoo, and Seung Yun Yang in article number 1600361.

In this study, we developed coordinative amphiphiles for use as novel siRNA transporters. As a modification of a conventional cationic lipid structure, we replaced the cationic head with zinc(II)-dipicolylamine complex (Zn/DPA) as a phosphate-directing group, and used various membrane-directing groups in the place of the hydrophobic tails. These simple amphiphiles are readily synthesized and easy to modify. The Zn/DPA head groups bind to the phosphate backbones of siRNAs, and to our surprise, they prevented the enzymatic degradation of siRNAs by RNase A. Interestingly, the Zn/DPA head itself exhibited moderate transfection efficiency, and its combination with a membrane-directing group-oleoyl (CA1), pyrenebutyryl (CA2), or biotin (CA3)-enhanced the delivery efficiency without imparting significant cytotoxicity. Notably, the uptake pathway was tunable depending on the nature of the membrane-directing group. CA1 delivered siRNAs mainly through caveolae-mediated endocytosis, and CA2 through clathrin- and caveolin-independent endocytosis; CA3 recruited siRNAs specifically into biotin receptor-positive HepG2 cells through receptor-mediated endocytosis. Thus, it appears possible to develop tunable siRNA transporters simply by changing the membrane-directing parts. These are the first examples of amphiphilic siRNA transporters accompanying coordinative interactions between the amphiphiles and siRNAs.

We report a simple and facile strategy for the preparation of multifunctional nanoparticles with programmable properties using self-assembly of precisely designed block amphiphiles in an aqueous solution-state. Versatile, supramolecular nanoplatform for personalized needs, particularly-theranostics, was fabricated by coassembly of peptide amphiphiles (PAs) in aqueous solution, replacing time-consuming and inaccessible chemical synthesis. Fibrils, driven by the assembly of hydrophobic β-sheet-forming peptide block, were utilized as a nanotemplate for drug loading within their robust core. PAs were tagged with octreotide [somatostatin (SST) analogue] for tumor-targeting or were conjugated with paramagnetic metal ion (Gd)-chelating 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for magnetic resonance (MR) imaging. The two PA types were coassembled to integrate each PA function into original fibrillar nanotemplates. The adoption of a bulky target-specific cyclic octreotide and β-sheet-forming peptide with enhanced hydrophobicity led to a morphological transition from conventional fibrils to helical fibrils. The resulting one-dimensional nanoaggregates allowed the successful intracellular delivery of doxorubicin (DOX) to MCF-7 cancer cells overexpressing SST receptor (SSTR) and MR imaging by enabling high longitudinal (T) relaxivity of water protons. Correlation between the structural nature of fibrils formed by PA coassembly and contrast efficacy was elucidated. The coassembly of PAs with desirable functions may thus be a useful strategy for the generation of tailor-made biocompatible nanomaterials.

Carbon monoxide (CO) is recently accepted as a therapeutic molecule that exhibits remarkable biological actions, including anti-inflammation, antiapoptosis, and cytoprotection, at a physiological level. For clinical use without the side effect of tissue hypoxia, which arises from the uncontrolled administration of CO in the human body, CO-releasing molecules (CORMs) are developed to ensure safe and efficient CO-delivery. Herein, a syringe-injectable CO-releasing peptide hydrogel (COH) and a corresponding bioadhesive hydrogel patch (COHP), developed by rational supramolecular chemistry, to enhance the therapeutic efficacy of CO with controllable CO-release to a specific tissue is report. The injectable COH is prepared by self-assembly of the CORM-attached peptides with a gel-forming diphenylalanine-derivative, resulting in fibrillar networks and exhibiting prolonged CO-release compared with CORMs. Furthermore, Ca 2+ -chelating and mussel-derived catechol-functionalized peptides are introduced to afford a mechanically rigid, bioadhesive COHP that elicits cytoprotective and anti-inflammatory activities. The supramolecular COHP can be utilized in the efficient CO-delivery to the site of interest by conformal contacts, making it a promising scaffold for biomedical applications.

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Vertically aligned polymer nanopillar arrays on substrates are receiving increasing interest as functional surfaces for a broad range of applications. However, methods for preparing polymeric nanopillar arrays have poor controllability of dimensional parameters and are limited to few polymers. Here, a new method to prepare freestanding biodegradable nanopillar arrays on different substrates, including flexible sheets, by plasma etching with polystyrene‐block‐poly(acrylic acid) (PS‐PAA) block copolymer (BCP) micelles encapsulating Au nanoparticles (AuNP@PS‐PAA) is reported. The adsorption density of the AuNP@PS‐PAA micelles is controlled by the pH of the micelle solutions, affecting electrostatic interaction with the polyelectrolyte layers formed on a poly(lactic‐co‐glycolic acid) (PLGA) film coated on the substrates; thus, density‐controlled PLGA nanopillar arrays are prepared using the micelle array as an etching mask during plasma etching. The height of the PLGA nanopillars is controlled by adjusting the plasma etching time, achieving high aspect ratios (>10) on inch‐sized substrates. This new platform combining bottom‐up (controlling absorption of BCP micelles used as etching mask) and top‐down (plasma etching for nanopillar formation) approaches can be applied to prepare nanopillar arrays on substrates using different soft materials including biodegradable polymers.

In article number https://doi.org/10.1002/adfm.201803051, Eunji Lee and co‐workers present a therapeutic carbon monoxide (CO)‐releasing hydrogel patch obtained from self‐assembling rationally designed peptides. Controllable CO‐release elicits effective cytoprotective and anti‐inflammatory activities on mammalian tissues. The developed syringe‐injectable CO‐releasing peptide hydrogel and the corresponding bioadhesive hydrogel patch allow for localized application of therapeutic gas by injection or implantation into a tissue/organ of interest, providing new direction for regenerative medicine using gasotransmitters.