A Milk Extracellular Vesicle‐Based Nanoplatform Enhances Combination Therapy Against Multidrug‐Resistant Bacterial Infections DOI Creative Commons
Shaoqi Qu, Shuo Yang, Qingjun Xu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 25, 2024

Abstract The increasing occurrence of infections caused by multidrug‐resistant (MDR) bacteria drives the need for new antibacterial drugs. Due to current lack antibiotic discovery and development, strategies fight MDR are urgently needed. Efforts develop adjuvants increase effectiveness existing antibiotics design delivery systems essential address this issue. Here, a bioinspired system equipped with combination therapy paracellular transport is shown enhance efficacy against bacterial improving oral delivery. A screening platform established using an in vitro‐induced high polymyxin‐resistant strain acquire plumbagin, which enhances polymyxin. Functionalized milk extracellular vesicles (FMEVs) coloaded polymyxin plumbagin cleared 99% within 4 h. Mechanistic studies revealed that drug damaged membrane, disrupted energy metabolism, accelerated death. Finally, FMEVs efficiently transported transcellularly through citric acid‐mediated reversible opening tight junctions showed Escherichia coli ‐associated peritonitis–sepsis model mice. These findings provide potential therapeutic strategy improve enhancing biomimetic platform.

Language: Английский

Understanding the toxicological effects of TiO2 nanoparticles extracted from sunscreens on human keratinocytes and skin explants DOI Creative Commons

Darien Yu De Kwek,

Magdiel Inggrid Setyawati, Archana Gautam

et al.

Particle and Fibre Toxicology, Journal Year: 2024, Volume and Issue: 21(1)

Published: Dec. 4, 2024

Inorganic ultraviolet filters such as titanium dioxide nanoparticles are frequently used in sunscreens. Numerous toxicological studies vitro and vivo have been conducted using pristine standard reference nanomaterials of these inorganic filters. While convenient, this approach is not realistic because the complex environment sunscreen formulations could change physicochemical properties lead to vastly different outcomes. Therefore, study focused on characterizing extracted from commercial evaluating associated impacts upon exposure human keratinocytes skin explants. Titanium were sunscreens thoroughly characterized. The identity molecular corona was also evaluated. Cell metabolic proliferation profiles, mitochondrial superoxide activity, reactive oxygen species levels, genotoxicity induced through studied a keratinocyte cell line. response significantly after treatment with compared corresponding sunscreen-extracted nanoparticles. Pristine spherical resulted more pronounced toxicity 2D cultured but did impact wound-edge migration 3D ex explant models. Additionally, rod-shaped had greater toxic retarded model Nevertheless, heightened responses any increase phosphorylated γH2AX (which indicative DNA damage) both vivo. This shows feasibility extracting personal care products obtain relevant forms real-life scenarios. Overall, found be less equivalents significantly. Skin cultures provide alternative monolayer cultures, although differential outcomes between models need in-depth evaluation.

Language: Английский

Citations

2

Insights into Tumor Size-Dependent Nanoparticle Accumulation Using Deformed Organosilica Nanoprobes DOI
Yuchen Miao,

Hengda Du,

Wenqing Zhang

et al.

Materials Chemistry Frontiers, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Deformed organosilica nanoprobes (CDPF) exhibit enhanced accumulation within larger tumors, highlighting the pivotal role of tumor microenvironment in optimization nanoparticle-based therapeutic strategies.

Language: Английский

Citations

1

Peptide-Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic β-Cell DOI
Jillian Collins, Jessie M. Barra,

Keifer Holcomb

et al.

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 7(10), P. 6451 - 6466

Published: Sept. 24, 2024

Targeting current therapies to treat or prevent the loss of pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off-target effects. Current efforts target β-cell are limited by a lack β-cell-specific targets inability test multiple targeting moieties with same delivery vehicle. Here, we fabricate tailorable polycaprolactone nanocapsule (NC) which different peptides can be interchangeably attached for delivery. Incorporation cationic surfactant NC shell allows attachment Exendin-4 an antibody ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3) targeting. The average size ranges from 250 300 nm polydispersity index under 0.2. NCs nontoxic, stable media culture, lyophilized reconstituted. coated peptide were taken up human cadaveric stem cell-derived β-like cells (sBC) vitro high level specificity. Furthermore, successfully delivered both hydrophobic hydrophilic cargo β-cells. Additionally, Exendin-4-coated targeted mouse vivo. Overall, our have potential improve cell-targeted drug utilized as screening platform cell-targeting peptides.

Language: Английский

Citations

1

Peptide Coated Polycaprolactone-Benzalkonium Chloride Nanocapsules for Targeted Drug Delivery to the Pancreatic β-Cell DOI
Jillian Collins, Jessie M. Barra,

Kiefer Holcomb

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

Targeting of current therapies to treat or prevent loss pancreatic islet β-cells in Type 1 Diabetes (T1D) may provide improved efficacy and reduce off target effects. Current efforts the β-cell are limited by a lack specific targets inability test multiple targeting moieties with same delivery vehicle. Here we fabricate novel tailorable polycaprolactone nanocapsule (NC) where different peptides can be interchangeably attached for delivery. Incorporation cationic surfactant NC shell allows attachment Exendin-4 an antibody ectonucleoside triphosphate diphosphohydrolase 3 (ENTPD3) targeting. The average size ranges from 250-300nm polydispersity index under 0.2. NCs non-toxic, stable media culture, lyophilized reconstituted. coated peptide were taken up human cadaveric stem cell-derived β-like cells (sBC)

Language: Английский

Citations

0

Towards a Switchable Nanoparticle Behavior Using Inverse Electron-Demand Diels-Alder Chemistry and Ectoenzyme-Based Ligand Activation DOI Creative Commons
Johannes Lang, Kathrin Schorr,

Achim Goepferich

et al.

European Journal of Pharmaceutical Sciences, Journal Year: 2024, Volume and Issue: unknown, P. 106944 - 106944

Published: Oct. 1, 2024

Language: Английский

Citations

0

A Milk Extracellular Vesicle‐Based Nanoplatform Enhances Combination Therapy Against Multidrug‐Resistant Bacterial Infections DOI Creative Commons
Shaoqi Qu, Shuo Yang, Qingjun Xu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 25, 2024

Abstract The increasing occurrence of infections caused by multidrug‐resistant (MDR) bacteria drives the need for new antibacterial drugs. Due to current lack antibiotic discovery and development, strategies fight MDR are urgently needed. Efforts develop adjuvants increase effectiveness existing antibiotics design delivery systems essential address this issue. Here, a bioinspired system equipped with combination therapy paracellular transport is shown enhance efficacy against bacterial improving oral delivery. A screening platform established using an in vitro‐induced high polymyxin‐resistant strain acquire plumbagin, which enhances polymyxin. Functionalized milk extracellular vesicles (FMEVs) coloaded polymyxin plumbagin cleared 99% within 4 h. Mechanistic studies revealed that drug damaged membrane, disrupted energy metabolism, accelerated death. Finally, FMEVs efficiently transported transcellularly through citric acid‐mediated reversible opening tight junctions showed Escherichia coli ‐associated peritonitis–sepsis model mice. These findings provide potential therapeutic strategy improve enhancing biomimetic platform.

Language: Английский

Citations

0