3 research outputs found
Preparation of poly-l-lysine-based nanoparticles with pH-sensitive release of curcumin for targeted imaging and therapy of liver cancer <i>in vitro</i> and <i>in vivo</i>
<p>Poly-l-lysine (PLL) nanoparticle (NP) system was prepared for the controlled release of curcumin (CUR) by pH stimuli, and its theranostic efficacy on cancer was compared to that of CUR solution <i>in vitro</i> and <i>in vivo</i>. Deoxycholic acid (DOCA), methoxy polyethylene glycol (MPEG) and cyanine 5.5 (cy5.5) were conjugated to the amine group of PLL through condensation reaction (PLL-DOCA-MPEG-cy5.5), followed by encapsulation of CUR by dialysis method (PLL-DOCA-MPEG-cy5.5/CUR NPs). The composition, morphology and size distribution of PLL-DOCA-MPEG-cy5.5 NPs were characterized by proton nuclear magnetic resonance (<sup>1</sup>H NMR), transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. <i>In vitro</i> tests exhibited that changes in the charge and size of the NPs at low pH led to the improved cellular uptake of CUR into human hepatoma Hep3B cell line by electrostatically absorptive endocytosis. PEGylation with MPEG was turn out to be very effective to have a prolonged blood circulation time, in turn increased the EPR effect. In addition, the incorporation of Cy5.5 into NPs provided successful biodistribution images <i>in vivo</i> and <i>ex vivo</i>. Our findings suggest that PLL-DOCA-MPEG-cy5.5/CUR NPs may have promising applications in cancer theranosis.</p
Detection of Active Matrix Metalloproteinase‑3 in Serum and Fibroblast-Like Synoviocytes of Collagen-Induced Arthritis Mice
The activity of rheumatoid arthritis
(RA) correlates with the expression
of proteases. Among several proteases, matrix metalloproteinase-3
(MMP-3) is one of the biological markers used to diagnose RA. The
active form of MMP-3 is a key enzyme involved in RA-associated destruction
of cartilage and bone. Thus, detection of active MMP-3 in serum or <i>in vivo</i> is very important for early diagnosis of RA. In
this study, a soluble MMP-3 probe was prepared to monitor RA progression
by detecting expression of active MMP-3 in collagen-induced arthritis
(CIA) mice <i>in vivo</i> in both serum and fibroblast-like
synoviocytes (FLSs). The MMP-3 probe exhibited strong sensitivity
to MMP-3 and moderate sensitivity to MMP-7 at nanomolecular concentrations,
but was not sensitive to other MMPs such as MMP-2, MMP-9, and MMP-13.
In an optical imaging study, the MMP-3 probe produced early and strong
NIR fluorescence signals prior to observation of erythema and swelling
in CIA mice. The MMP-3 probe was able to rapidly and selectively detect
and monitor active MMP-3 in diluted serum from CIA mice. Furthermore,
histological data demonstrated that activated FLSs in arthritic knee
joints expressed active MMP-3. Together, our results demonstrated
that the MMP-3 probe may be useful for detecting active MMP-3 for
diagnosis of RA. More importantly, the MMP-3 probe was able to detect
active MMP-3 in diluted serum with high sensitivity. Therefore, the
MMP-3 probe developed in this study may be a very promising probe,
useful as a biomarker for early detection and diagnosis of RA
Prediction of Antiarthritic Drug Efficacies by Monitoring Active Matrix Metalloproteinase‑3 (MMP-3) Levels in Collagen-Induced Arthritic Mice Using the MMP‑3 Probe
Active matrix metalloproteinase-3
(MMP-3) is a prognostic marker
of rheumatoid arthritis (RA). We recently developed an MMP-3 probe
that can specifically detect the active form of MMP-3. The aim of
this study was to investigate whether detection and monitoring of
active MMP-3 could be useful to predict therapeutic drug responses
in a collagen-induced arthritis (CIA) model. During the period of
treatment with drugs such as methotrexate (MTX) or infliximab (IFX),
MMP-3 mRNA and protein levels were correlated with fluorescence signals
in arthritic joint tissues and in the serum of CIA mice. Also, bone
volume density and erosion in the knee joints and the paws of CIA
mice were measured with microcomputed tomography (micro-CT), X-ray,
and histology to confirm drug responses. In joint tissues and serum
of CIA mice, strong fluorescence signals induced by the action of
active MMP-3 were significantly decreased when drugs were applied.
The decrease in RA scores in drug-treated CIA mice led to fluorescence
reductions, mainly as a result of down-regulation of MMP-3 mRNA or
protein. The micro-CT, X-ray, and histology results clearly showed
marked decreases in bone and cartilage destruction, which were consistent
with the reduction of fluorescence by down-regulation of active MMP-3
in drug-treated CIA mice. We suggest that the MMP-3 diagnostic kit
could be used to detect and monitor the active form of MMP-3 in CIA
mice serum during a treatment course and thereby used to predict the
drug response or resistance to RA therapies at an earlier stage. We
hope that monitoring of active MMP-3 levels in arthritis patients
using the MMP-3 diagnostic kit will be a promising tool for drug discovery,
drug development, and monitoring of drug responses in RA therapy