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

• Published in: Biomacromolecules Vol. 24; no. 2; pp. 1003 - 1013
• Main Authors: Bi, Feihu, Zhang, Jin, Xie, Rui, Yu, Deshui, Wei, Hanchen, Wang, Yulong, Hua, Zan, Qi, Xiangming, Huang, Bo, Yang, Guang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13.02.2023
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacteria; beta-Cyclodextrins - pharmacology; Escherichia coli; Glycoconjugates - chemistry; Glycoconjugates - pharmacology; Hemolysis; Humans
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.2c01440

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.