Tandem Peptide Approaches for Delivery to Gram-Negative Bacteria

Technology

This technology works by coupling a membrane-interacting peptide to a microbial agent which may also be formulated with a carrier such as a porous silicon nanoparticle, polymer nanoparticle, liposome, or dextran molecule for in vivo delivery. Once released, the membrane-interacting peptide associates with the bacterial membrane, increasing local concentration of the bactericidal domain at the cell surface and enabling efficient disruption of the bacterium while minimizing damage to healthy tissue. In some embodiments, association with the prokaryotic membrane induces a change in membrane structure, such as pore formation, allowing translocation of the antimicrobial agent. Compared with conventional antibiotics and free antimicrobial peptides, this targeted delivery strategy is designed to improve antimicrobial activity, reduce off-toxicity, and treat Gram-negative bacterial infections.  

Problem Addressed

The rise of antibiotic-resistant bacteria, combined with the limited development of new antibacterial drugs, has created an urgent need for alternative strategies to treat bacterial infections. Antimicrobial peptides are promising because they can selectively interact with bacterial membranes, act rapidly, and be engineered for therapeutic use, but their clinical application has been limited by poor bacterial penetration, reduced in vivo activity, and off-target toxicity. This technology overcomes these challenges by combining a highly potent tandem antimicrobial peptide with a biodegradable porous silicon nanoparticle carrier that localizes the therapy to infected lung tissue and provides controlled peptide release. Together, this approach improves antibacterial efficacy while reducing toxicity, offering a potential new treatment option for drug-resistant Gram-negative infections.

Advantages

• The membrane-interacting peptide helps deliver the antimicrobial agent to Gram-negative bacterial membranes, enabling selective antibacterial activity with low mammalian cell toxicity. 
• By using a membrane-targeted mechanism rather than relying solely on conventional antibiotic targets, the technology offers a promising strategy to combat antibiotic-resistant bacterial infections.    
• The membrane-targeting peptide and bactericidal peptide act synergistically, producing substantially greater antibacterial activity than either component alone. 
• The antimicrobial constructs are modular and can incorporate different membrane-targeting peptides, antimicrobial payloads, and targeting moieties, enabling the platform to target a range of bacterial pathogens and therapeutic applications.