Biomacromolecules Update: Welcome to Our New Editors and New Procedure for Review Submission

Despite the pandemic and the difficulties posed by it to researchers around the world, 2020 has been a great year for Biomacromolecules as it achieved some significant milestones in the past year. First, Biomacromolecules reached the highest level in history with a record impact factor of above 6.0. Furthermore, what a year I have had! I have truly enjoyed my first year as Editor-in-Chief. Thanks to all at the ACS, from the journal office to production to marketing to the leadership at ACS Publications, for making the transition smooth and providing me all the support to continue to expand the influence of Biomacromolecules. A special thanks to our Managing Editor, Dr. Paulomi Majumder, for her unwavering support. In an effort to provide our community with fast, smooth, fair, and ethical editing and review processes, we have implemented and continue to implement several processes. For instance, we now have established a new procedure to optimize the process for a review proposal. Even if the majority of reviews are solicited by members of the editorial board in accordance with editorial policy, the editorial office welcomes suggestions for reviews that may be suitable for the journal

Controlling Polymersome Size through Microfluidic-Assisted Self-Assembly: Enabling 'Ready to Use' formulations for biological applications

The self-assembly of poly(ethylene glycol)-block-poly(trimethylene carbonate) PEG-b-PTMC copolymers into vesicles, also referred as polymersomes, was evaluated by solvent displacement using microfluidic systems. Two microfluidic chips with different flow regimes (micromixer and Herringbone) were used and the impact of process conditions on vesicle formation was evaluated. As polymersomes are sensitive to osmotic variations, their preparation under conditions allowing their direct use in biological medium is of major importance. We therefore developed a solvent exchange approach from DMSO (Dimethylsulfoxide) to aqueous media with an osmolarity of 300 mOsm.L-1, allowing their direct use for biological evaluation. We evidenced that the organic/aqueous solvent ratio does not impact vesicle size, but the total flow rate and copolymer concentration have been observed to influence the size of polymersomes. Finally, nanoparticles with diameters ranging from 76 nm to 224 nm were confirmed to be vesicles through the use of multi-angle light scattering in combination with cryo-TEM (Cryo-Transmission Electron Microscopy) characterization

Multivalent Elastin-Like Glycopolypeptides: Subtle Chemical Structure Modifications with High Impact on Lectin Binding Affinity

A library of synthetic elastin-like glycopolypeptides were synthesized and screened by microscale thermophoresis to identify key structural parameters affecting lectin binding efficacy. While polypeptide backbone size and glycovalency were found to have little influence, the presence of a linker at the anomeric position of galactose and the absence of positive charge on the polypeptide residue holding the sugar unit were found to be critical for the binding to RCA120.Développement de squelettes polypeptidiques recombinants pour la synthèse de glycoconjugués multivalents parfaitement défini

Avidin Localizations in pH-Responsive Polymersomes for Probing the Docking of Biotinylated (Macro)molecules in the Membrane and Lumen

To mimic organelles and cells and to construct next-generation therapeutics, asymmetric functionalization and location of proteins for artificial vesicles is thoroughly needed to emphasize the complex interplay of biological units and systems through spatially separated and spatiotemporal controlled actions, release, and communications. For the challenge of vesicle (= polymersome) construction, the membrane permeability and the location of the cargo are important key characteristics that determine their potential applications. Herein, an in situ and post loading process of avidin in pH-responsive and photo-cross-linked polymersomes is developed and characterized. First, loading efficiency, main location (inside, lumen, outside), and release of avidin under different conditions have been validated, including the pH-stable presence of avidin in polymersomes’ membrane outside and inside. This advantageous approach allows us to selectively functionalize the outer and inner membranes as well as the lumen with several bio(macro)molecules, generally suited for the construction of asymmetrically functionalized artificial organelles. In addition, a fluorescence resonance energy transfer (FRET) effect was used to study the permeability or uptake of the polymersome membrane against a broad range of biotinylated (macro)molecules (different typology, sizes, and shapes) under different conditions

Biomacromolecules

Three-dimensional (3D) bioprinting offers a great alternative to traditional techniques in tissue reconstruction, based on seeding cells manually into a scaffold, to better reproduce organs' complexity. When a suitable bioink is engineered with appropriate physicochemical properties, such a process can advantageously provide a spatial control of the patterning that improves tissue reconstruction. The design of an adequate bioink must fulfill a long list of criteria including biocompatibility, printability, and stability. In this context, we have developed a bioink containing a precisely controlled recombinant biopolymer, namely, elastin-like polypeptide (ELP). This material was further chemoselectively modified with cross-linkable moieties to provide a 3D network through photopolymerization. ELP chains were additionally either functionalized with a peptide sequence Gly-Arg-Gly-Asp-Ser (GRGDS) or combined with collagen I to enable cell adhesion. Our ELP-based bioinks were found to be printable, while providing excellent mechanical properties such as stiffness and elasticity in their cross-linked form. Besides, they were demonstrated to be biocompatible, showing viability and adhesion of dermal normal human fibroblasts (NHF). Expressions of specific extracellular matrix (ECM) protein markers as pro-collagen I, elastin, fibrillin, and fibronectin were revealed within the 3D network containing cells after only 18 days of culture, showing the great potential of ELP-based bioinks for tissue engineering

Refining the Design of Diblock Elastin-Like Polypeptides for Self-Assembly into Nanoparticles

Diblock copolymers based-on elastin-like polypeptide (ELP) have the potential to undergo specific phase transitions when thermally stimulated. This ability is especially suitable to form carriers, micellar structures for instance, for delivering active cargo molecules. Here, we report the design and study of an ELP diblock library based on ELP-[M1V3-i]-[I-j]. First, ELP-[M1V3-i]-[I-j] (i = 20, 40, 60; j = 20, 90) that showed a similar self-assembly propensity (unimer-to-aggregate transition) as their related monoblocks ELP-[M1V3-i] and ELP-[I-j]. By selectively oxidizing methionines of ELP-[M1V3-i] within the different diblocks structures, we have been able to access a thermal phase transition with three distinct regimes (unimers, micelles, aggregates) characteristic of well-defined ELP diblocks.Nanomedicine: an integrative approac

Cyclic Poly(α-peptoid)s by Lithium bis(trimethylsilyl)amide (LiHMDS)-Mediated Ring-Expansion Polymerization: Simple Access to Bioactive Backbones

Cyclic polymers display unique physicochemical and biological properties. However, their development is often limited by their challenging preparation. In this work, we present a simple route to cyclic poly(α-peptoids) from N-alkylated-N-carboxyanhydrides (NNCA) using LiHMDS promoted ring-expansion polymerization (REP) in DMF. This new method allows the unprecedented use of lysine-like monomers in REP to design bioactive macrocycles bearing pharmaceutical potential against Clostridioides difficile, a bacterium responsible for nosocomial infections

Synthesis, self-assembly, and immunological activity of α-galactose-functionalized dendron–lipid amphiphiles

Nanoassemblies presenting multivalent displays of biologically active carbohydrates are of significant interest for a wide array of biomedical applications ranging from drug delivery to immunotherapy. In this study, glycodendron–lipid hybrids were developed as a new and tunable class of dendritic amphiphiles. A modular synthesis was used to prepare dendron–lipid hybrids comprising distearylglycerol and 0 through 4th generation polyester dendrons with peripheral protected amines. Following deprotection of the amines, an isothiocyanate derivative of C-linked α-galactose (α-Gal) was conjugated to the dendron peripheries, affording amphiphiles with 1 to 16 α-Gal moieties. Self-assembly in water through a solvent exchange process resulted in vesicles for the 0 through 2nd generation systems and micelles for the 3rd and 4th generation systems. The critical aggregation concentrations decreased with increasing dendron generation, suggesting that the effects of increasing molar mass dominated over the effects of increasing the hydrophilic weight fraction. The binding of the assemblies to Griffonia simplicifolia Lectin I (GSL 1), a protein with specificity for α-Gal was studied by quantifying the binding of fluorescently labeled assemblies to GSL 1-coated beads. It was found that binding was enhanced for amphiphiles containing higher generation dendrons. Despite their substantial structural differences with the natural ligands for the CD1d receptor, the glycodendron–lipid hybrids were capable of stimulating invariant natural killer T (iNKT) cells, a class of innate-like T cells that recognize lipid and glycolipid antigens presented by CD1d and that are implicated in a wide range of diseases and conditions including but not limited to infectious diseases, diabetes and cancer

Synthetic Glycopolypeptides as Biomimetic Analogues of Natural Glycoproteins

Glycoproteins are naturally produced by protein glycosylation and are involved in a wide range of cellular functions. This Review aims to summarize the preparation of well-defined synthetic glycoproteins by using chemical routes as well as to highlight the preparation of ideal polymeric analogues of natural glycoproteins: glycopolypeptides. These macromolecules are simplified models of glycoproteins and are designed with the purpose of both mimicking the properties of natural glycoproteins as well as bringing innovative polymeric structures for materials science applications

Magnetic polymer 'nanopills'

With specialist knowledge of polymer-based, self-assembled nanoparticles, the Laboratoire de Chimie des Polymères Organiques shares developments in polymer synthesis and polymer materials. We are a group of 5 tenured academic researchers and about 15 non-permanent researchers in the Laboratoire de Chimie des Polymères Organiques, a joint research unit of CNRS, University of Bordeaux, and Bordeaux National Polytechnic Institute, dedicated to polymer synthesis and polymer materials. More precisely, our group develops polymer-based self-assembled nanoparticles with high loading rates of active pharmaceutical ingredient (anticancer drugs, peptides, proteins...), multi-modal labelling (MRI, NIR...) and targeting (e.g. mAb). Our know-how includes the synthesis of biocompatible polymers such as polypeptides (by chemical synthesis or recombinant route), polysacharrides, and their combination as copolymers. We have a more than 1 decade experience in the design of multifunctional polymer vesicles called "polymersomes" loaded with drugs, iron oxide nanoparticles, grafted to antibodies, and several patents including one licensed to a pharmaceutical company located in Lyon (Adocia). We have some experience as participant in European projects, including a FP7 large NMP project (NANOTHER), which led to very promising results and productive interactions with biomedical companies, and we are now seeking to be active partners of a new H2020 project on nanomedicine.Magnéto-Chimiothérapie : Modélisation de la Délivrance Induite par Champ Magnétique Radiofréquence d'Anticancéreux par des Nano-Vésicules Polymères et Suivi par IRM d'un Modèle de GlioblastomeIntegration of Novel Nanoparticle based Technology for Therapeutics and Diagnosis of different types of Cance