Pyridine-containing block copolymers are a special type of macromolecules, and they can self-assemble into highly-ordered nano-objects for a wide range of applications due to their multiple properties including the hydrogen...
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 β-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 dyeloaded 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-1β) 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.
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 β-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.
The development of smart and controllable multivalent systems, which enable us to control the interactions at the biological system-artificial material interface, is of great scientific and technological interest. In this...
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