Structure-Controllable and Mass-Produced Glycopolymersomes as a Template of the Carbohydrate@Ag Nanobiohybrid with Inherent Antibacteria and Biofilm Eradication.

Glycopolymer-supported silver nanoparticles (AgNPs) have demonstrated a promising alternative to antibiotics for the treatment of multidrug-resistant bacteria-infected diseases. In this contribution, we report a class of biohybrid glycopolymersome-supported AgNPs, which are capable of effectively killing multidrug-resistant bacteria and disrupting related biofilms. First of all, glycopolymersomes with controllable structures were massively fabricated through reversible addition-fragmentation chain transfer (RAFT) polymerization-induced self-assembly (PISA) in an aqueous solution driven by complementary hydrogen bonding interaction between the pyridine and amide groups of N-(2-methylpyridine)-acrylamide (MPA) monomers. Subsequently, Ag+ captured by glycopolymersomes through the coordination between pyridine-N and Ag+ was reduced into AgNPs stabilized by glycopolymersomes upon addition of the NaBH4 reducing agent, leading to the formation of the glycopolymersome@AgNPs biohybrid. As a result, they showed a wide-spectrum and enhanced removal of multidrug-resistant bacteria and biofilms compared to naked AgNPs due to the easier adhesion onto the bacterial surface and diffusion into biofilms through the specific protein-carbohydrate recognition. Moreover, the in vivo results revealed that the obtained biohybrid glycopolymersomes not only demonstrated an effective treatment for inhibiting the cariogenic bacteria but also were able to repair the demineralization of caries via accumulating Ca2+ through the recognition between carbohydrates and Ca2+. Furthermore, glycopolymersomes@AgNPs showed quite low in vitro hemolysis and cytotoxicity and almost negligible acute toxicity in vivo. Overall, this type of biohybrid glycopolymersome@AgNPs nanomaterial provides a new avenue for enhanced antibacterial and antibiofilm activities and the effective treatment of oral microbial-infected diseases.

Adenosine Triphosphate-Responsive Glyconanorods through Self-Assembly of ß-Cyclodextrin-Based Glycoconjugates for Targeted and Effective Bacterial Sensing and Killing.

Polymer-based nanomaterials have exhibited promising alternative avenues to combat the globe challenge of multidrug-resistant bacterial infection. However, most of the reported polymeric nanomaterials have facially linear amphiphilic structures with positive net charges, which may lead to nonspecific binding, high hemolysis, and uncontrollable self-organization, limiting their practical applications. In this contribution, we report a one-dimensional glyconanorod (GNR) through self-assembly of well-defined ß-cyclodextrin-based glycoconjugates (RMan) featuring hydrophobic carbon-based chains and amide rhodamines with an adenosine triphosphate (ATP)-recognition site and targeted and hydrophilic mannoses and positively net-charged ethylene amine groups. The GNRs show superior targeting sensing and killing for Gram-negative Escherichia coli (E. coli) dominantly through the multivalent recognition between mannoses on the nanorod and the lectin on the surface of E. coli. Moreover, red fluorescence was light on due to the hydrogen bonding between amide rhodamine and ATP. Benefiting from the designs, the GNRs are capable of possessing a higher therapeutic index and of encapsulating other antibiotics. They exhibit an enhanced effect against E. coli strains. Intriguingly, the GNRs displayed a more reduced hemolysis effect and lower cytotoxicity compared to that of ethylene glyco-modified nanorods. These results reveal that the glyconanomaterials not only feature superior and targeted bacterial sensing and antibacterial activity, but also better biocompatibility compared with the widely used PEG-covered nanomaterials. Furthermore, the in vivo studies demonstrate that the targeted and ATP-responsive GNRs complexed with antibiotics showed better treatment using a mouse model of abdominal sepsis following intraperitoneal E. coli infection. The present work describes a targeted and effective sensing and antibacterial platform based on glycoconjugates that have potential applications for the treatment of infections caused by pathogenic microorganisms.

Dynamic Glycopeptide Dendrimers: Synthesis and Their Controllable Self-Assembly into Varied Glyco-Nanostructures for the Biomimicry of Glycans.

A library of 14 dynamic glycopeptide amphiphilic dendrimers composed of 14 hydrophilic and bioactive saccharides (seven kinds) as dendrons and 7 hydrophobic peptides (di- and tetrapeptides) as arms with ß-cyclodextrin (CD) as a core were facially designed and synthesized in several steps. Fourteen saccharides were first conjugated to the C-2 and C-3 positions of CD, forming glycodendrons. Subsequently, seven oligopeptide arms were introduced at the C-6 positions of a CD moiety by an acylhydrazone dynamic covalent bond, resulting in unique Janus amphiphilic glycopeptide dendrimers with precise and varied molecular structures. The kinds of hydrophilic parts of saccharides and hydrophobic parts of peptides were easily varied to prepare a series of amphiphilic Janus glycopeptide dendrimers. Intriguingly, these obtained amphiphilic glycopeptide dendrimers showcased very different self-assembly behaviors from the traditional amphiphilic linear block-copolymers and self-assembled into different glyco-nanostructures with controllable morphologies including glycospheres, worm-like micelles, and fibers depending upon the repeat unit ratio of saccharides and phenylalanine. Both glycodendrons and glycopeptide assemblies displayed strong and specific recognitions with C-type mannose-specific lectin. Moreover, these glycopeptide nanomaterials can encapsulate exemplary hydrophobic molecules such as Nile red (NR). The dye-loaded glycopeptide nanostructures showed a pH-controllable release behavior around the physiological and acidic tumor environment. Furthermore, cell experiments demonstrated that such glyco-nanostructures can further facilitate the functions of a model drug of the pyridone agent to reduce the expression of monocyte chemotactic protein-1 (MCP-1) and interleukin -1beta (IL-1ß) in the primary peritoneal macrophages via encapsulating drugs. Considering all the abovementioned advantages including unique and precise structures, bioactivity, targeting, and controllable cargo release, we believe that these findings can not only enrich the library of glycopeptides but also provide a new avenue to the fabrication of smart and structure-controllable glyco-nanomaterials which hold great potential biological applications such as targeted delivery and release of therapeutic and bioactive molecules.

Morphological Transformation and Surface Engineering of Glycovesicles Driven by Bioinspired Hydrogen Bonds of Nucleobases.

Glycopolymer-based supramolecular glycoassemblies with signal-driven cascade morphological deformation and accessible surface engineering toward bioinspired functional glycomaterials have attracted much attention due to their diverse applications in fundamental and practical scenarios. Herein, we achieved the cascade morphological transformation and surface engineering of a nucleobase-containing polymeric glycovesicle through exploiting the bioinspired complementary multiple hydrogen bonds of complementary nucleobases. First, the synthesized thymine-containing glycopolymers (PGal30-b-PTAm249) are capable of self-assembling into well-defined glycovesicles. Several kinds of amphiphilic adenine-containing block copolymers with neutral, positive, and negative charges were synthesized to engineer the glycovesicles through the multiple hydrogen bonds between adenine and thymine. A cascade of morphological transformations from vesicles to ruptured vesicles with tails, to worm-like micelles, and finally to spherical micelles were observed via continuously adding the adenine-containing polymer into the thymine-containing glycovesicles. Furthermore, the surface charge properties of these glyconano-objects can be facilely regulated through incorporating various adenine-containing polymers. This work demonstrates the potential application of a unique bioinspired approach to precisely engineer the morphology and surface properties of glycovesicles for boosting their biological applications.

Core-Shell Polymeric Nanostructures with Intracellular ATP-Fueled dsRNA Delivery toward Genetic Control of Insect Pests.

Transgenic RNA interference (RNAi) represents a burgeoning and promising alternative avenue to manage plant diseases and insect pests in plants. Nonviral nanostructured dsRNA carriers have been demonstrated to possess great potential to facilitate the application of RNAi. However, it remains a critical challenge to achieve the targeted and effective release of dsRNA into the pest cells, limiting the efficiency of the biological control of pests and diseases in practical applications. In this study, we designed and constructed a new type of core-shell polymeric nanostructure (CSPN) with controllable structure, eco-friendliness, and good biocompatibility, on which dsRNA can be efficiently loaded. Once loaded into CSPNs, the dsRNA can be effectively prevented from nonsense degradation by enzymes before entering cells, and it shows targeted and image-guided release triggered by intracellular ATP, which significantly increases the efficiency of gene transfection. Significantly, the in vivo study of the typical lepidoptera silkworm after oral feeding demonstrates the potential of dsCHT10 in CSPNs for a much better knockdown efficiency than that of naked dsCHT10. This innovation enables the nanotechnology developed for the disease microenvironment-triggered release of therapeutic genes for application in sustainable crop protection.