Graft-through ring-opening metathesis polymerization (ROMP) of norbornene-terminated macromonomers (MMs) prepared using various polymerization methods has been extensively used for the synthesis of bottlebrush (co)polymers, yet the potential of ROMP for the synthesis of MMs that can subsequently be polymerized by graft-through ROMP to produce new bottlebrush compositions remains untapped. Here, we report an efficient "ROMP-of-ROMP" method that involves the synthesis of norbornene-terminated poly(norbornene imide) (PNI)-based MMs that, following ROMP, provide new families of bottlebrush (co)polymers and "brush-on-brush" hierarchical architectures. In the bulk state, the organization of the PNI pendants drives bottlebrush backbone extension to enable rapid assembly of asymmetric lamellar morphologies with large asymmetry factors. Overall, this work expands the scope of complex macromolecular architectures and provides insights into the interplay of backbone rigidity and self-assembly that will guide future nanolithography applications.
Controlling the access of proteases to cleavable peptides placed at specific locations within macromolecular architectures represents a powerful strategy for biologically responsive materials design. Here, we report the synthesis of peptide-containing bivalent bottlebrush (co)polymers (BBPs) featuring polyethylene glycol (PEG) and 7-amino-4-methylcoumarin (AMC) pendants on each backbone repeat unit. The AMCs are linked via caspase-3-cleavable peptides which, upon enzymatic cleavage, provide a "turn-on" fluorescence signal due to the release of free AMC. Time-dependent fluorscence measurements demonstrate that the caspase-3-induced peptide cleavage and AMC release from BBPs is strongly dependent on the BBP backbone length and the AMC–peptide linker location within the BBP architecture, revealing fundamental insights into the interactions of enzymes with BBPs.
Amphiphilic homopolymers with high densities of functional groups are synthetically challenging. Thiol-yne nucleophilic click reactions have been investigated to introduce multiple functional groups in polymers with high density. An electron deficient alkyne group bearing methacrylate monomer was polymerized using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Subsequently, the electron deficient alkyne group on polymer side chain was readily reacted with a thiol reagent using triethylamine (TEA) as the organocatalyst. This reaction was found to be very efficient under mild conditions. The resultant homopolymer bearing thiol vinyl ether functional groups could perform a second thiol addition with a stronger base, such as triazabicyclodecene (TBD), to prepare multifunctional homopolymers. This stepwise addition process was monitored by 1H NMR as well as gel permeation chromatography. The fidelity of this method was demonstrated by attaching four different functionalities, including both hydrophobic and hydrophilic moieties. Furthermore, these dual functionalized polymers bearing dithio-acetal groups are sensitive to reactive oxygen species (ROS), which compromises the host-guest properties of the assembly in response to this stimulus. The ROS responsive polymers reported here may have potential use in therapeutic delivery.
We developed a versatile and modular method for cytosolic protein delivery through metal ion-induced co-assembly of gold nanoclusters and proteins into supramolecular assemblies. The versatility and high efficiency of this strategy to assemble and deliver various proteins into living cells were demonstrated. Importantly, the activity of proteins was maintained during the delivery. This modular approach provides an exciting and promising new nano-platform for cytosolic protein delivery.
Abstract In this paper we report a novel DNA‐enrichment technology based on amino‐modified functionalized silica nanoparticles. The approach takes advantage of the amino‐modified silica nanoparticles that have been prepared in one step by the controlled synchronous hydrolysis of tetraethoxysilane and N‐(β‐amimoethyl)‐γ‐aminopropyltriethoxysilane in water nanodroplets of water‐in‐oil microemulsions. The functionalized silica nanoparticles display a positive surface charge at neutral pH due to the presence of amino groups on the surface of these nanoparticles. DNA‐enrichment has been realized in the form of nanoparticle–DNA complexes that is accomplished through electrostatic binding between the positive charge of the amino group and the negative charge of the phosphate groups of the nucleic acid. These nanoparticles have high affinity to bind DNA. The results show that 1 mg of nanoparticles can bind 97.2 µg of plasmid DNA with 4.3 kb. This novel DNA‐enrichment technology has been used successfully in gene delivery. Keywords: DNA‐enrichment technologyAmino‐modifiedSilica nanoparticlesGene delivery Acknowledgments This work was supported by the Pre‐Key Project of Basic Research of the Sci. and Tec. Ministry of China (2001‐51), Key Project of Natural Science Foundation of P.R. China (20135010), Key Project Foundation of China Education Ministry (2000‐156), Oversea Youth Scholar Co‐research Foundation of P.R. China (20028506), and National Key Basic Research Program (2002CB513100).
Abstract Polymer–drug conjugates are promising as strategies for drug delivery, because of their high drug loading capacity and low premature release profile. However, the preparation of these conjugates is often tedious. In this paper, we report an efficient method for polymer–drug conjugates using an ultrafast and reversible click reaction in a post‐polymerization functionalization strategy. The reaction is based on the rapid condensation of boronic acid functionalities with salicylhydroxamates. The polymer, bearing the latter functionality, has been designed such that the reaction with boronic acid bearing drugs induces an in situ self‐assembly of the conjugates to form well‐defined nanostructures. We show that this method is not only applicable for molecules with an intrinsic boronic acid group, but also for the other molecules that can be linked to aryl boronic acids through a self‐immolative linker. The linker has been designed to cause traceless release of the attached drug molecules, the efficiency of which has been demonstrated through intracellular delivery.
Designer nanomaterials capable of delivering immunomodulators to specific immune cells have been extensively studied. However, emerging evidence suggests that several of these nanomaterials can nonspecifically activate NLRP3 inflammasomes, an intracellular multiprotein complex controlling various immune cell functions, leading to undesirable effects. To understand what nanoparticle attributes activate inflammasomes, we designed a multiparametric polymer supramolecular nanoparticle system to modulate various surface and core nanoparticle-associated molecular patterns (NAMPs), one at a time. We also investigated several underlying signaling pathways, including lysosomal rupture-cathepsin B maturation and calcium flux-mitochondrial ROS production, to gain mechanistic insights into NAMPs-mediated inflammasome activation. Here, we report that out of the four NAMPs tested, core hydrophobicity strongly activates and positively correlates with the NLRP3 assembly compared to surface charge, core rigidity, and surface hydrophobicity. Moreover, we demonstrate different signaling inclinations and kinetics followed by differential core hydrophobicity patterns with the most hydrophobic ones exhibiting both lysosomal rupture and calcium influx early on. Altogether, this study will help design the next generation of polymeric nanomaterials for specific regulation of inflammasome activation, aiding efficient immunotherapy and vaccine delivery.
Metallacycloaddition: Eine neuartige formale [4+2]-Cycloaddition läuft ab, wenn das Osmiumhydrido(alkenylcarbin) 1 mit Acetonitril umgesetzt wird. Der in hoher Ausbeute gebildete erste Metallapyridiniumkomplex 2 (siehe Schema) liefert beim Deprotonieren die erste Osmapyridinverbindung 3. Durch Behandeln von 3 mit HBF4 kann 2 nahezu quantitativ zurückgebildet werden. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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