Molecular Self-Assembly and Supramolecular Chemistry of Cyclic Peptides.

This Review focuses on the establishment and development of self-assemblies governed by the supramolecular interactions between cyclic peptides. The Review first describes the type of cyclic peptides able to assemble into tubular structures to form supramolecular cyclic peptide nanotubes. A range of cyclic peptides have been identified to have such properties, including α-peptides, ß-peptides, α,γ-peptides, and peptides based on δ- and ε-amino acids. The Review covers the design and functionalization of these cyclic peptides and expands to a recent advance in the design and application of these materials through their conjugation to polymer chains to generate cyclic peptide-polymer conjugates nanostructures. The Review, then, concentrates on the challenges in characterizing these systems and presents an overview of the various analytical and characterization techniques used to date. This overview concludes with a critical survey of the various applications of the nanomaterials obtained from supramolecular cyclic peptide nanotubes, with a focus on biological and medical applications, ranging from ion channels and membrane insertion to antibacterial materials, anticancer drug delivery, gene delivery, and antiviral applications.

Supra-Cyanines: Ultrabright Cyanine-Based Fluorescent Supramolecular Materials in Solution and in the Solid State.

Fluorescent materials with high brightness play a crucial role in the advancement of various technologies such as bioimaging, photonics, and OLEDs. While significant efforts are dedicated to designing new organic dyes with improved performance, enhancing the brightness of existing dyes holds equal importance. In this study, we present a simple supramolecular strategy to develop ultrabright cyanine-based fluorescent materials by addressing long-standing challenges associated with cyanine dyes, including undesired cis-trans photoisomerization and aggregation-caused quenching. Supra-cyanines are obtained by incorporating cyanine moieties in a cyclic peptide-based supramolecular scaffold, and exhibit high fluorescence quantum yields (up to 50 %) in both solution and in the solid state. These findings offer a versatile approach for constructing highly emissive cyanine-based supramolecular materials.

Looking beyond leaves: variation in nutrient leaching potential of seasonal litterfall among different species within an urban forest.

Urban litterfall that is deposited on impervious surface leaches nutrients into stormwater, contributing to downstream eutrophication. Previous studies have focused on the leaching potential of deciduous leaf litter, while other smaller-volume litterfall types-such as blossoms and fruit-may leach significant amounts of nitrogen, phosphorus, and carbon. These additional litterfall types represent an unaccounted-for source of nutrients to urban stormwater. We explored variation in leaching potential of dissolved nutrients and organic carbon across litter types and species by collecting litterfall (blossoms, fruit, leaves) from ten common urban tree species. After 24 h of leaching, we measured total phosphorus (TP), total dissolved nitrogen (TDN), and dissolved organic carbon (DOC) contributions and compared differences across litter types and species. Litter basket estimates then allowed us to quantify annual litterfall inputs. We found that blossoms leached 3-20 times more TDN and 1.5-7 times more TP than leaves of the same species. Furthermore, considering litterfall mass, several species had greater springtime nutrient-leaching potential compared to fall due to high leaching potential in blossoms and lower potential in leaves. We found mixed effects of leaf crushing and leachate solution (stormwater, salinity) on leaching rates. This study highlights the need to consider all litterfall types as well as variation in urban forest communities and conditions when seeking to budget, control, and maintain for potential nutrient sources from the urban forest. Supplementary information: The online version contains supplementary material available at 10.1007/s11252-022-01217-8.

Modular design of cyclic peptide - polymer conjugate nanotubes for delivery and tunable release of anti-cancer drug compounds.

High aspect-ratio nanomaterials have recently emerged as promising drug delivery vehicles due to evidence of strong cellular association and prolonged in vivo circulation times. Cyclic peptide - polymer conjugate nanotubes are excellent candidates due to their elongated morphology, their supramolecular composition and high degree of pliability due to the versatility in manipulating amino acid sequence and polymer type. In this work, we explore the use of a nanotube structure on which a potent anti-cancer drug, camptothecin, is attached alongside hydrophilic or amphiphilic RAFT polymers, which shield the cargo. We show that subtle modifications to the cleavable linker type and polymer architecture have a dramatic influence over the rate of drug release in biological conditions. In vitro studies revealed that multiple cancer cell lines in 2D and 3D models responded effectively to the nanotube treatment, and analogous fluorescently labelled materials revealed key mechanistic information regarding the degree of cellular uptake and intracellular fate. Importantly, the ability to instruct specific drug release profiles indicates a potential for these nanomaterials as vectors which can provide sustained drug concentrations for a maximal therapeutic effect.

Supra-Fluorophores: Ultrabright Fluorescent Supramolecular Assemblies Derived from Conventional Fluorophores in Water.

Fluorescent organic nanoparticles (NPs) with exceptional brightness hold significant promise for demanding fluorescence bioimaging applications. Although considerable efforts are invested in developing novel organic dyes with enhanced performance, augmenting the brightness of conventional fluorophores is still one of the biggest challenges to overcome. This study presents a supramolecular strategy for constructing ultrabright fluorescent nanoparticles in aqueous media (referred to as "Supra-fluorophores") derived from conventional fluorophores. To achieve this, this course has employed a cylindrical nanoparticle with a hydrophobic microdomain, assembled by a cyclic peptide-diblock copolymer conjugate in water, as a supramolecular scaffold. The noncovalent dispersion of fluorophore moieties within the hydrophobic microdomain of the scaffold effectively mitigates the undesired aggregation-caused quenching and fluorescence quenching by water, resulting in fluorescent NPs with high brightness. This strategy is applicable to a broad spectrum of fluorophore families, covering polyaromatic hydrocarbons, coumarins, boron-dipyrromethenes, cyanines, xanthenes, and squaraines. The resulting fluorescent NPs demonstrate high fluorescence quantum yield (>30%) and brightness per volume (as high as 12 060 m-1 cm-1 nm-3). Moreover, high-performance NPs with emission in the NIR region are constructed, showcasing up to 20-fold increase in both brightness and photostability. This Supra-fluorophore strategy offers a versatile and effective method for transforming existing fluorophores into ultrabright fluorescent NPs in aqueous environments, for applications such as bioimaging.

The over-expression of cell migratory genes in alveolar rhabdomyosarcoma could contribute to metastatic spread.

Alveolar (ARMS) and Embryonal (ERMS) rhabdomyosarcoma differ in their response to current treatments. The ARMS subtype has a less favourable prognosis and often presents with widespread metastases, while the less metastatic ERMS has a 5 year survival rate of more than 80 %. In this study we investigate gene expression differences that could contribute to the high frequency of metastasis in ARMS. Microarray analysis identified significant differences in DNA repair, cell cycle and cell migration between the two RMS subtypes. Two genes up regulated in ARMS and involved in cell migration; the engulfment and cell motility gene 1 (ELMO1) and NEL-like 1 gene (NELL1) were selected for further investigation. Over-expression of ELMO1 significantly increased cell invasion from 24.70 ± 7% to 93 ± 5.4% in primary myoblasts and from 29.43 ± 2.1% to 87.33 ± 4.1% in the ERMS cell line RD. siRNA knockout of ELMO1 in the ARMS cell line RH30 significantly reduced cell invasion from 88.2 ± 3.8% to 35.2 ± 2.5%. Over-expression of NELL1 significantly increased myoblast invasion from 23.6 ± 6.9% to 100 ± 0.1%, but had no effect on invasion of the ERMS cell line RD. These findings suggest that ELMO1 may play a key role in ARMS metastasis. NELL1 increased invasion in primary myoblasts, but other factors required for it to enhance motility were not present in the RD ERMS cell line. Impairing ELMO1 function by pharmacological or siRNA knockdown could be a highly effective approach to reduce the metastatic spread of RMS.