Due
to the abuse of antibiotics, antimicrobial resistance is rapidly
emerging and becoming a major global risk for public health. Thus,
there is an urgent need for reducing the use of antibiotics, finding
novel treatment approaches, and developing controllable release systems.
In this work, a dual synergistic antibacterial platform with on-demand
release ability based on silver nanoparticles (AgNPs) and antimicrobial
peptide (AMP) coloaded porous silicon (PSi) was developed. The combination
of AgNPs and AMPs (Tet-213, KRWWKWWRRC) exhibited an excellent synergistic
antibacterial effect. As a carrier, porous silicon can efficiently
load AgNPs and AMP under mild conditions and give the platform an
on-demand release ability and a synergistic release effect. The AgNPs
and AMP coloaded porous silicon microparticles (AgNPs-AMP@PSiMPs)
exhibited an acid pH and reactive oxygen species (ROS)-stimulated
release of silver ions (Ag+) and AMPs under bacterial infection
conditions because of oxidation and desorption effects. Moreover,
the release of the bactericide could be promoted by each other due
to the interplay between AgNPs and Tet-213. In vitro antibacterial tests demonstrated that AgNPs-AMP@PSiMPs inherited
the intrinsic properties and synergistic antibacterial efficiency
of both bactericides. In addition, wound dressing loaded with AgNPs-AMP@PSiMPs
showed outstanding in vivo bacteria-killing activity,
accelerating wound-healing, and low biotoxicity in aStaphylococcus aureus-infected rat wound model. The
present work demonstrated that PSiMPS might be an efficient platform
for loading the antibiotic-free bactericide, which could synergistically
and on-demand release to fight wound infection and promote wound healing.
Spatially resolved tissue lipidomics
is essential for accurate
intraoperative and postoperative cancer diagnosis by revealing molecular
information in the tumor microenvironment. Matrix-free laser desorption
ionization mass spectrometry imaging (LDI-MSI) is an emerging attractive
technology for label-free visualization of metabolites distributions
in biological specimens. However, the development of LDI-MSI technology
that could conveniently and authentically reveal molecular distribution
on tissue samples is still a challenge. Herein, we present a tissue
imprinting technology by retaining tissue lipids on 2D nanoflakes-capped
silicon nanowires (SiNWs) for further mass spectrometry imaging and
cancer diagnosis. The 2D nanoflakes were prepared by liquid exfoliation
of molybdenum disulfide (MoS2) with nitrogen-doped graphene
quantum dots (NGQDs), which serve as both intercalation agent and
dispersant. The obtained NGQD@MoS2 nanoflakes were then
decorated on the tip of vertical SiNWs, forming a hybrid NGQD@MoS2/SiNWs nanostructure, which display excellent lipid extraction
ability, enhanced LDI efficiency and molecule imaging capability.
The peak number and total ion intensity of different lipids species
on animal lung tissues obtained by tissue imprinting LDI-MSI on NGQD@MoS2/SiNWs were ∼4–5 times greater than those on
SiNWs substrate. As a proof-of-concept demonstration, the NGQD@MoS2/SiNWs nanostructure was further applied to visualize phospholipids
on sliced non small cell lung cancer (NSCLC) tissue along with the
adjacent normal tissue. On the basis of selected feature lipids and
machine learning algorithm, a prediction model was constructed to
discriminate NSCLC tissues from the adjacent normal tissues with an
accuracy of 100% for the discovery cohort and 91.7% for the independent
validation cohort.
Serum
lipid metabolites have been emerging as ideal biomarkers
for disease diagnosis and prediction. In the current stage, nontargeted
or targeted lipidomic research mainly relies on a liquid chromatography–mass
spectrometry (LC–MS) platform, but future clinical applications
need more robust and high-speed platforms. Surface-assisted laser
desorption ionization mass spectrometry (SALDI-MS) has shown excellent
advantages in the high-speed analysis of lipid metabolites. However,
the platform in the positive ion mode is more inclined to target a
certain class of lipids, leading to the low coverage of lipid detection
and limiting its practical translation to clinical applications. Herein,
we proposed a dual-mechanism-driven strategy for high-coverage detection
of serum lipids on a novel SALDI-MS target, which is a composite nanostructure
comprising vertical silicon nanowires (VSiNWs) decorated with AuNPs
and polydopamine (VSiNW-Au-PDA). The performance of laser desorption
and ionization on the target can be enhanced by charge-driven desorption
coupled with thermal-driven desorption. Simultaneous detection of
236 serum lipids (S/N ≥ 5) including neutral and polar lipids
can be achieved in the positive ion mode. Among these, 107 lipid peaks
were successfully identified. When combined with VSiNW-Au-PDA and
VSiNW chips, 479 lipid peaks can be detected in serum samples in positive
and negative ion modes, respectively. Based on the platform, serum
samples from 57 hepatocellular carcinoma (HCC) patients and 76 healthy
controls were analyzed. After data mining, 14 lipids containing different
lipid types (TAG, CE, PC) were selected as potential lipidomic biomarkers.
With the assistance of an artificial neural network, a diagnostic
model with a sensitivity of 92.7% and a specificity of 96% was constructed
for HCC diagnosis.
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