Microbial resistance is one of the main problems of modern medicine. Recently, antimicrobial peptides have been recognized as a novel approach to overcome the microbial resistance issue, nevertheless, their low stability, toxicity, and potential immunogenic response in biological systems have limited their clinical application. Herein, we present the design, synthesis, and preliminary biological evaluation of polymer-antibacterial peptide constructs. The antimicrobial GKWMKLLKKILK-NH2 oligopeptide (PEP) derived from halictine, honey bee venom, was bound to a polymer carrier via various biodegradable spacers employing the pH-sensitive or enzymatically-driven release and reactivation of the PEP’s antimicrobial activity. The antibacterial properties of the polymer-PEP constructs were assessed by a determination of the minimum inhibitory concentrations, followed by fluorescence and transmission electron microscopy. The PEP exerted antibacterial activity against both, gram-positive and negative bacteria, via disruption of the bacterial cell wall mechanism. Importantly, PEP partly retained its antibacterial efficacy against Staphylococcus epidermidis, Escherichia coli, and Acinetobacter baumanii even though it was bound to the polymer carrier. Indeed, to observe antibacterial activity similar to the free PEP, the peptide has to be released from the polymer carrier in response to a pH decrease. Enzymatically-driven release and reactivation of the PEP antimicrobial activity were recognized as less effective when compared to the pH-sensitive release of PEP.

No abstract

Nano‐sized carriers are widely studied as suitable candidates for the advanced delivery of various bioactive molecules such as drugs and diagnostics. Herein, the development of long‐circulating stimuli‐responsive polymer nanoprobes tailored for the fluorescently‐guided surgery of solid tumors is reported. Nanoprobes are designed as long‐circulating nanosystems preferably accumulated in solid tumors due to the Enhanced permeability and retention effect, so they act as a tumor microenvironment‐sensitive activatable diagnostic. This study designs polymer probes differing in the structure of the spacer between the polymer carrier and Cy7 by employing pH‐sensitive spacers, oligopeptide spacers susceptible to cathepsin B‐catalyzed enzymatic hydrolysis, and non‐degradable control spacer. Increased accumulation of the nanoprobes in the tumor tissue coupled with stimuli‐sensitive release behavior and subsequent activation of the fluorescent signal upon dye release facilitated favorable tumor‐to‐background ratio, a key feature for fluorescence‐guided surgery. The probes show excellent diagnostic potential for the surgical removal of intraperitoneal metastasis and orthotopic head and neck tumors with very high efficacy and accuracy. In addition, the combination of macroscopic resection followed by fluorescence‐guided surgery using developed probes enable the identification and resection of most of the CAL33 intraperitoneal metastases with total tumor burden reduced to 97.2%.