Hydrophobic modification improves the delivery of cell-penetrating peptides to eliminate intracellular pathogens in animals

Tang, Qi; Tan, Peng; Dai, Zhaolai; Wang, Tao; Xu, Shenrui; Ding, Yakun; Jin, Junhua; Zhang, Xin; Zhang, Yucheng; Zhou, Chenlong; Yue, Zitian; Fu, Hong; Jiang, Yan; Ma, Xi

doi:10.1016/j.actbio.2022.11.055

Cited by 21 publications

(16 citation statements)

References 57 publications

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“…The mechanism of action of peptide nanofibers against Gram-negative bacteria is mainly to combine with LPS to reduce the metabolic circulation of endotoxin in vivo . This mechanism may also limit the immunogenic potential of piglets . The normalization of proinflammatory cytokines factors suggests that peptide nanofibers have not only direct antimicrobial but also some immunomodulatory properties, and they work together in the treatment of systemic bacterial infections in sepsis.…”

Section: Results and Discussionmentioning

confidence: 99%

“…This mechanism may also limit the immunogenic potential of piglets. 8 The normalization of proinflammatory cytokines factors suggests that peptide nanofibers have not only direct antimicrobial but also some immunomodulatory properties, and they work together in the treatment of systemic bacterial infections in sepsis. To further visualize infection in organ tissues, we performed H&E staining of tissue sections.…”

Section: 5mentioning

confidence: 99%

“…7 AMPs have emerged as a promising alternative to antibiotics in the treatment of pathogenic infections. 8 However, the high toxicity, susceptibility to physiological environment, and expensive production cost of natural AMPs make them unsuitable as optimal antibacterial drugs, limiting their availability. 9 Supramolecular nanofibers based on β-sheet peptide assemblies have gained significance in biomedical fields but have not been widely explored as antimicrobial nanomaterials.…”

Section: Introductionmentioning

confidence: 99%

“…AMPs have emerged as a promising alternative to antibiotics in the treatment of pathogenic infections . However, the high toxicity, susceptibility to physiological environment, and expensive production cost of natural AMPs make them unsuitable as optimal antibacterial drugs, limiting their availability .…”

Section: Introductionmentioning

confidence: 99%

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Design of High-Selectivity Co-Assembled Peptide Nanofibers against Bacterial Infection in Piglets

Tan

Tang

et al. 2023

ACS Appl. Mater. Interfaces

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Antibiotic resistance is an escalating global health concern that could result in tens of millions of deaths annually from drug-resistant bacterial infections in the future, especially in animal husbandry. Peptide antibacterial nanomaterials offer a competitive alternative to antibiotics because of their distinct mechanism of physically penetrating pathogenic biological membranes. This study developed amphiphilic co-assembled peptide nanofibers with high biological selectivity (PCBP-NCAP NFs) to overcome the high cytotoxicity of peptide PCBP and the low antibacterial activity of peptide NCAP. PCBP-NCAP NFs exhibit broad-spectrum antibacterial activity and excellent biocompatibility, with negligible in vivo and in vitro toxicity. Additionally, PCBP-NCAP NFs possess direct antibacterial efficacy and potential immunomodulatory capabilities using a piglet systemic infection model. Its unique mechanism of membrane penetration and the ability to bind to anionic components on the surface of pathogenic bacteria make them less susceptible to drug resistance. In conclusion, these findings have significant implications for the advancement of supramolecular peptide nanomedicines for clinical application and animal husbandry.

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Section: Results and Discussionmentioning

confidence: 99%

Section: 5mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Design of High-Selectivity Co-Assembled Peptide Nanofibers against Bacterial Infection in Piglets

Tan

Tang

et al. 2023

ACS Appl. Mater. Interfaces

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“…For instance, chimeric antibiotics containing a macrocycle of polymyxin B exhibit potent activity against major Gramnegative members of multidrug-resistant (MDR) bacterial pathogens and overcome colistin resistance. 10 Furthermore, the reported intracellular delivery approaches such as carrier-mediated delivery systems or cell-penetrating peptides are very effective in intracellular drug delivery, [11][12][13] but they are non-tunable and can result in a specific scope of application, significantly limiting the utility of these carriers as potent tools against intracellular bacterial infections. The encapsulated antibiotics target bacterial colonies hidden in intracellular compartments, which is the critical step in the elimination of intracellular bacteria.…”

Section: Kui Zhumentioning

confidence: 99%

Endocytosis-mediated redistribution of antibiotics targets intracellular bacteria

Zhu

2023

Nanoscale

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pH‐Triggered Size‐Transformable and Bioactivity‐Switchable Self‐Assembling Chimeric Peptide Nanoassemblies for Combating Drug‐Resistant Bacteria and Biofilms

Tan

Tang

et al. 2023

Advanced Materials

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Drug‐resistant bacteria and biofilm‐associated infections are prominent problems in the field of antibacterial medicine, seriously affecting human and animal health. Despite the great potential of nanomaterials in the antibacterial field, overcoming the paradox of size and charge, efficient penetration, and retention within biofilms remain a formidable challenge. Here, self‐assembling chimeric peptide nanoassemblies composed of multiple functional fragments are designed for the treatment of drug‐resistant bacteria and biofilm‐associated infections. Notably, the chimeric peptide self‐assembles into nanofibers at pH 7.4 and is transformable into nanoparticles in the acidic biofilm‐infected microenvironment at pH 5.0, and thus achieves a size reduction and charge increase, improving the penetration into the bacterial biofilms and killing drug‐resistant bacteria by a mechanism dominated by membrane cleavage. In vivo mouse and piglet infection models confirm the ability of chimeric peptide nanoassemblies to reduce bacterial load within biofilms. Collectively, this research on pathological‐environment‐driven nanostructural transformations may provide a theoretical basis for designing high‐performance antibacterial nanomaterials and advance the application of peptide‐based nanomaterials in medicine and animal husbandry.

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Hydrophobic modification improves the delivery of cell-penetrating peptides to eliminate intracellular pathogens in animals

Cited by 21 publications

References 57 publications

Design of High-Selectivity Co-Assembled Peptide Nanofibers against Bacterial Infection in Piglets

Design of High-Selectivity Co-Assembled Peptide Nanofibers against Bacterial Infection in Piglets

Endocytosis-mediated redistribution of antibiotics targets intracellular bacteria

pH‐Triggered Size‐Transformable and Bioactivity‐Switchable Self‐Assembling Chimeric Peptide Nanoassemblies for Combating Drug‐Resistant Bacteria and Biofilms

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