Polymer nanomedicines with enzymatically triggered activation: A comparative study of in vitro and in vivo anti-cancer efficacy related to the spacer structure

Pechar, Michal; Pola, Robert; Studenovský, Martin; Blahová, M; Grosmanová, Eliška; Dydowiczová, Aneta; Filipová, Marcela; Islam, Rayhanul; Gao, Shanghui; Fang, Jun; Etrych, Tomáš

doi:10.1016/j.nano.2022.102597

Cited by 4 publications

(1 citation statement)

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“…Moreover, the nondegradable β-Ala spacer was employed in a stable P-PEP construct as the control system. Recently, the ValCit spacer was introduced as a suitable spacer for the controlled release of the cytostatics [ 30 ], thus it was also applied in this study. Since bacterial infection and biofilm formation may lower the pH in the infected site, a pH-responsive hydrazone bond was introduced as well into the polymer-AMP construct to investigate the benefits of pH-sensitive release and re-activation of the AMP ( Figure 4 A).…”

Section: Resultsmentioning

confidence: 99%

Polymer-Antimicrobial Peptide Constructs with Tailored Drug-Release Behavior

et al. 2023

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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.

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Section: Resultsmentioning

confidence: 99%