3 years ago

An “On-Site Transformation” Strategy for Treatment of Bacterial Infection

An “On-Site Transformation” Strategy for Treatment of Bacterial Infection
Hao Wang, Guo-Bin Qi, Fu-Hua Liu, Zeng-Ying Qiao, Di Zhang
To date, numerous nanosystems have been developed as antibiotic replacements for bacterial infection treatment. However, these advanced systems are limited owing to their nontargeting accumulation and the consequent side effects. Herein, transformable polymer–peptide biomaterials have been developed that enable specific accumulation in the infectious site and long-term retention, resulting in enhanced binding capability and killing efficacy toward bacteria. The polymer–peptide conjugates are composed of a chitosan backbone and two functional peptides, i.e., an antimicrobial peptide and a poly(ethylene glycol)-tethered enzyme-cleavable peptide (CPC-1). The CPC-1 initially self-assembles into nanoparticles with pegylated coronas. Upon the peptides are cleaved by the gelatinase secreted by a broad spectrum of bacterial species, the resultant compartments of nanoparticles spontaneously transformed into fibrous nanostructures that are stabilized by enhanced chain–chain interaction, leading to exposure of antimicrobial peptide residues for multivalent cooperative electrostatic interactions with bacterial membranes. Intriguingly, the in situ morphological transformation also critically improves the accumulation and retention of CPC-1 in infectious sites in vivo, which exhibits highly efficient antibacterial activity. This proof-of-concept study demonstrates that pathological environment-driven smart self-assemblies may provide a new idea for design of high-performance biomaterials for disease diagnostics and therapeutics. Transformable chitosan–peptide biomaterials (CPC-1) initially self-assemble into nanoparticles with pegylated coronas. Upon cleavage of the peptides by gelatinase, the resultant compartments of nanoparticles spontaneously transform into fibrous nanostructures. The in situ morphological transformation critically improves the accumulation and retention of CPC-1 in infectious sites in vivo, which exhibits highly efficient antibacterial activity.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adma.201703461

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