Antisense Oligonucleotides Selectively Enter Human‐Derived Antibiotic‐Resistant Bacteria through Bacterial‐Specific ATP‐Binding Cassette Sugar Transporter

Abstract

Current vehicles used to deliver antisense oligonucleotides (ASOs) cannot distinguish between bacterial and mammalian cells, greatly hindering the preclinical or clinical treatment of bacterial infections, especially those caused by antibiotic‐resistant bacteria. Herein, bacteria‐specific ATP‐binding cassette (ABC) sugar transporters are leveraged to selectively internalize ASOs by hitchhiking them on α (1–4)‐glucosidically linked glucose polymers. Compared with their cell‐penetrating peptide counterparts, which are non‐specifically engulfed by mammalian and bacterial cells, the presented therapeutics consisting of glucose polymer and antisense peptide nucleic‐acid‐modified nanoparticles are selectively internalized into the human‐derived multidrug‐resistant Escherichia coli and methicillin‐resistant Staphylococcus aureus, and they display a much higher uptake rate (i.e., 51.6%). The developed strategy allows specific and efficient killing of nearly 100% of the antibiotic‐resistant bacteria. Its significant curative efficacy against bacterial keratitis and endophthalmitis is also shown. This strategy will expand the focus of antisense technology to include bacterial cells other than mammalian cells.

Photoactivated Gas-Generating Nanocontrast Agents for Long-Term Ultrasonic Imaging-Guided Combined Therapy of Tumors

“…First, generality of the constructed PGNAs was evaluated (Figure a), for which three similar types of NPs with spherical nanostructure, namely, silicon nanoparticles (SiNPs) with a diameter of ∼4.19 nm (Figure S1a), gold nanoparticles (AuNPs) with a diameter of ∼4.85 nm (Figure S2a), and poly­(lactic- co -glycolic acid) (PLGA) nanoparticles with a diameter of ∼58.77 nm (Figure S3a), were synthesized to serve as the core NPs. − Next, the as-prepared NPs were respectively loaded with ABC and Ce6 molecules, followed by coating with a PDA shell to form the final PGNAs. These PGNAs presented diameters of ∼18.17 nm [for Si PGNAs] (Figure S1a), ∼11.70 nm [for Au PGNAs] (Figure S2a), or ∼68.06 nm [for PLGA PGNAs] (Figure S3a), which were much larger than those of the free SiNPs, AuNPs, or PLGA, respectively.…”

Subtractive modification of bacterial consortium using antisense peptide nucleic acids

“… Równicki et al (2017) synthesized a conjugate of vitamin B 12 and PNA, which was successfully taken up by Escherichia coli and Salmonella Typhimurium cells via the vitamin B 12 uptake pathway. Liu et al (2023) also synthesized a conjugate of glucose polymer and PNA, and the conjugate was delivered into the E. coli and Staphylococcus aureus cells through the ABC sugar transporter pathway. Among these carriers, cell-penetrating peptides (CPP), which are short cationic peptides and facilitate the cellular uptake of biomolecules, has been used for the longest time and applied to many microorganisms.…”

Coordination-Driven Self-Assembly of Metal Ion–Antisense Oligonucleotide Nanohybrids for Chronic Bacterial Infection Therapy

“…By addressing the aforementioned barriers, these nanoparticle-based approaches overcome challenges in the field of biotherapeutics. − Compared with other methods of drug therapy or research, antisense nucleic acid technology offers advantages such as simple synthesis, high specificity, and the ability to inhibit gene expression. As a result, it has garnered significant attention and interest among researchers and has found widespread applications in the fields of anticancer and antibacterial research. − The ftsZ gene encodes the filament temperature-sensitive protein Z (FtsZ), which plays a critical role as a cytoskeletal protein in bacterial cytoplasmic division machinery . Inhibition of the ftsZ gene expression can enhance bactericidal effects .…”