Activatable prodrug for controlled release of an antimicrobial peptide via the proteases overexpressed inCandida albicansandPorphyromonas gingivalis DOI Open Access
Lubna Amer, Maurice Retout, Jesse V. Jokerst

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 27, 2023

ABSTRACT We report the controlled release of an antimicrobial peptide using enzyme-activatable prodrugs to treat and detect Candida albicans Porphyromonas gingivalis . Our motivation lies in prevalence these microorganisms subgingival area where frequency fungal colonization increases with periodontal disease. This work is based on that both therapeutic induces a color change nanoparticle reporter. was then built into zwitterionic prodrug quenches its activity until activation by protease inherent pathogens interest: SAP9 or RgpB for C. P. , respectively. first confirmed intact has negligible toxicity fungal, bacterial, mammalian cells absent trigger. Next, impact assessed via disk diffusion viability assays showed minimum inhibitory concentration 3.1 – 16 µg/mL, which comparable alone (absent integration prodrug). Finally, design exploited colorimetric detection proteases. When were cleaved, plasmonic nanoparticles aggregated causing limit 10 nM gold 3 silver nanoparticles. approach value as convenient selective sensing protease-induced treatment mechanism bioinspired peptides. Abstract Figure

Language: Английский

Colorimetric sensing for translational applications: from colorants to mechanisms DOI
Zhicheng Jin, Wonjun Yim, Maurice Retout

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(15), P. 7681 - 7741

Published: Jan. 1, 2024

This review summarizes insights into colorant selection and signal mechanisms for the development of colorimetric sensing POC sensors.

Language: Английский

Citations

37

Silver Nanoparticle Sensor Array for the Detection of SARS-CoV-2 DOI
Benjamin Lam, Maurice Retout, Alex E. Clark

et al.

ACS Applied Nano Materials, Journal Year: 2024, Volume and Issue: 7(8), P. 9136 - 9146

Published: April 15, 2024

We report a silver nanoparticle (AgNP) sensor array to detect SARS-CoV-2 viral particles utilizing five peptide receptors produce colorimetric response. show that the interaction of virus with peptides interferes shift in plasmonic absorbance and hinders formation snowflake-like fractal assemblies between AgNPs bridging peptides. The limit detection water was 500,000 copies/mL. demonstrate capabilities distinguish (Beta, Delta, Omicron variants) from influenza at 99% confidence level through linear discriminant analysis. also able discriminate three out negative exhaled breath condensate samples positive EBC samples.

Language: Английский

Citations

8

Activatable prodrug for controlled release of an antimicrobial peptide via the proteases overexpressed in Candida albicans and Porphyromonas gingivalis DOI Creative Commons
Lubna Amer, Maurice Retout, Jesse V. Jokerst

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(4), P. 1781 - 1793

Published: Jan. 1, 2024

Candida albicans and Porphyromonas gingivalis are prevalent in the subgingival area where frequency of fungal colonization increases with periodontal disease.Candida's transition to a pathogenic state its interaction P. exacerbate disease severity.However, current treatments for these infections differ, combined therapy remains unexplored.This work is based on an antimicrobial peptide that therapeutic induces color change nanoparticle reporter.Methods: We built characterized two enzyme-activatable prodrugs treat detect C. via controlled release peptide.The zwitterionic prodrug quenches peptide's activity until activation by protease inherent pathogens (SAP9 RgpB gingivalis).The toxicity intact was evaluated against fungal, bacterial, mammalian cells.Therapeutic efficacy assessed through microscopy, disk diffusion, viability assays, comparing alone.Finally, we developed colorimetric detection system aggregation plasmonic nanoparticles.Results: The showed negligible cells absent trigger.The impact comparable alone, minimum inhibitory concentration 3.1 -16 µg/mL.The enzymatic returned limit 10 nM gold nanoparticles 3 silver nanoparticles.Conclusion: This approach offers convenient selective sensing protease-induced treatment mechanism bioinspired peptides.

Language: Английский

Citations

7

Cascaded Strand Displacement Amplification and CRISPR/Cas12a Aptasensor Utilizing MoS2 Nanoflowers for Colorectal Cancer Biomarker Porphyromonas gingivalis Detection DOI

Peiyi Zhang,

Shanshan Feng, Feng Liu

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Colorectal cancer (CRC) ranks as the third most prevalent globally, both in terms of diagnoses and cancer-related mortality. Increasing evidence suggests that an imbalance intestinal flora can contribute to progression CRC, fecal microbiota may serve potential biomarkers for its screening diagnosis. Notably, Porphyromonas gingivalis has been identified malignant tissues feces CRC patients, establishing it a significant biomarker early screening, diagnosis, prognostic assessment CRC. Current methods detecting P. face numerous challenges, including high costs, complex procedures, lengthy implementation times. Therefore, developing rapid, highly specific, sensitive detection is great importance. In this study, we utilized whole-bacterium systematic evolution ligands by exponential enrichment method identify specific high-affinity aptamers targeting through 15 selection cycles. Subsequently, developed aptasensor driven MoS2 nanoflowers, which integrates strand displacement amplification CRISPR/Cas12a double gingivalis, achieving limit 10 CFU/mL. Using aptasensor, evaluated abundance clinical samples observed significantly higher levels patients compared healthy individuals, corroborating results obtained from quantitative polymerase chain reaction. summary, first time, representing promising new approach identification with

Language: Английский

Citations

0

Activatable Photoacoustic Probe for Imaging Infection: Gold Nanorod Dissociation In Vivo Reports Bacterial Protease Activity DOI
Maurice Retout, Victor Lepeintre, Lubna Amer

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

We present a strategy for constructing activatable photoacoustic imaging (PAI) probes in vivo enzyme activity measurements, based on dissociation previously applied to vitro sensing. Unlike conventional nanoparticle aggregation strategies, minimizes false positives and functions effectively complex biological environments. Overcoming the challenge of dissociating nanostructure aggregates, which arises from strong van der Waals forces at short distances, we demonstrate controlled assembly citrate-capped gold nanorods (AuNRs-citrate) using diarginine peptide additive thiolated polyethylene glycol (HS-PEG-OMe), respectively. This mechanism enables precise control optical (PA) properties AuNRs both settings. Building these findings, engineered an enzyme-sensitive PAI probe (AuNRs@RgpB) composed AuNR assemblies PEG-peptide conjugate with protease-specific cleavage sequence. The detects Arg-specific gingipain (RgpB), protease expressed by Porphyromonas gingivalis associated periodontal disease Alzheimer's disease. Proteolytic sequence triggers dissociation, resulting enhanced PA signal output. was designed be injected intrathecally preclinical trials image gingipains investigate value inhibitors developed probe's performance characterized UV-vis spectroscopy PAI, achieving detection limits 5 20 nM, In studies involved intracranial injection AuNRs@RgpB into RgpB-containing murine models, monitoring over time. RgpB produced four-fold increase within 2 h, while P. gingivalis-infected mice showed similar enhancement. Specificity confirmed negligible responses Fusobacterium nucleatum, non-RgpB-producing bacterium. Additionally, system demonstrated utility drug development successfully inhibition (leupeptin KYT-1) models. Beyond its immediate application detection, this modular approach plasmonic-based sensing holds significant potential detecting other proteases, advancing nanotechnology protease-targeted diagnostics.

Language: Английский

Citations

0

A GMR enzymatic assay for quantifying nuclease and peptidase activity DOI Creative Commons

Michael Sveiven,

Ana K. Serrano,

Joshua V. Rosenberg

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2024, Volume and Issue: 12

Published: March 13, 2024

Hydrolytic enzymes play crucial roles in cellular processes, and dysregulation of their activities is implicated various physiological pathological conditions. These cleave substrates such as peptide bonds, phosphodiester glycosidic other esters. Detecting aberrant hydrolase activity vital for understanding disease mechanisms developing targeted therapeutic interventions. This study introduces a novel approach to measuring using giant magnetoresistive (GMR) spin valve sensors. sensors change resistance response magnetic fields, here, they are functionalized with specific hydrolases conjugated nanoparticles (MNPs). When cleaves its substrate, the tethered nanoparticle detaches, causing measurable shift sensor's resistance. design translates into real-time, activity-dependent signal. The assay simple, rapid, requires no washing steps, making it ideal point-of-care settings. Unlike fluorescent methods, avoids issues like autofluorescence photobleaching, broadening applicability diverse biofluids. Furthermore, sensor array contains 80 individually addressable sensors, allowing simultaneous measurement multiple single reaction. versatility this method demonstrated nucleases, Bcu I DNase I, peptidase, human neutrophil elastase. To demonstrate clinical application, we show that elastase sputum from cystic fibrosis patients hydrolyze peptide-GMR cleavage rate strongly correlates traditional fluorogenic substrate. innovative addresses challenges associated enzyme techniques, providing promising tool real-time quantification biological contexts.

Language: Английский

Citations

2

Biomolecule-regulation of fluorescent probe signaling: Homogeneous rapid portable protease sensing in serum DOI

Yalan Zhu,

Feng Pan,

Pengjun Jiang

et al.

Analytica Chimica Acta, Journal Year: 2024, Volume and Issue: 1316, P. 342824 - 342824

Published: June 6, 2024

Language: Английский

Citations

1

Mechanism of hierarchical plasmonic biomaterials engineered through peptide‐directed self‐assembly DOI Creative Commons
Lubna Amer, Maurice Retout, Zhicheng Jin

et al.

Aggregate, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 10, 2024

Abstract Hierarchical plasmonic biomaterials constructed from small nanoparticles (NPs) that combine into larger micron‐sized structures exhibit unique properties can be harnessed for various applications. Using diffusion‐limited aggregation (DLA) and defined peptide sequences, we developed fractal silver with a Brownian tree structure. This method avoids complex redox chemistry allows precise control of interparticle distance material morphology through design concentration. Our systematic investigation revealed how charge, length, sequence impact biomaterial morphology, confirming peptides act as bridging motifs between particles induce coalescence. Characterization spectroscopy microscopy demonstrated arginine‐based are optimal assembly based on both quantitative qualitative measurements. Additionally, our study diffusion behavior confirmed the effect particle size, temperature, medium viscosity nanoparticle mobility. work also provides insights facet distribution in NPs their mechanisms, offering potential advancements materials medical, environmental, electronic

Language: Английский

Citations

1

Peptide-Guided Assembly of Silver Nanoparticles for the Diagnosis of HER2-Positive Breast Cancer DOI
Qianxi Zhou,

Yuying Pan,

Qizhi Liang

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(49), P. 19304 - 19311

Published: Nov. 22, 2024

Peptide-engineered nanoparticles have great potential for biomedical research and application. In this work, we designed fabricated an electrochemical biosensor based on peptide-guided assembly of silver (AgNPs), in which a peptide is endowed with dual functions to recognize target guide AgNPs. As proof concept, the performance validated by quantifying human epidermal growth factor receptor 2 (HER2) protein. detail, end HER2-specific binding grafted positively charged peptide, can orderly AgNPs, while signals be obtained through phosphine-silver coordination. Using biosensor, HER2 protein quantified high sensitivity specificity, limit detection as low 0.05 pg/mL. Moreover, antifouling electrode surface prepared modification layer zwitterionic allows used serum from breast cancer patients, provides clear evidence distinction HER2+ patients HER2- patients.

Language: Английский

Citations

1

Matrix-Insensitive Sensor Arrays via Peptide-Coated Nanoparticles: Rapid Saliva Screening for Pathogens in Oral and Respiratory Diseases DOI
Benjamin Lam, Lubna Amer, Elizabeth Thompson

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Plasmonic nanoparticle-based biosensors often report a colorimetric signal through the aggregation or clustering of nanoparticles (NPs), but these mechanisms typically struggle to function in complex biofluids. Here, we matrix-insensitive sensor array approach detect bacteria, fungi, and viruses whose is based on dissociation peptide-aggregated NPs by thiolated polyethylene glycol (HS-PEG) polymers. We show that HS-PEGs differing sizes have varying capabilities dissociate citrate-capped gold nanoparticle (AuNP) silver (AgNP) assemblies. The dissociative abilities were used this discriminate at 90% confidence level microorganisms

Language: Английский

Citations

1