Thrombotic cardio-cerebrovascular diseases seriously threaten human health. Currently, conventional thrombolytic treatments are challenged by the low utilization, inferior thrombus penetration, and high off-target bleeding risks of most thrombolytic drugs, resulting in unsatisfactory treatment outcomes. Herein, it is proposed that these challenges can be overcome by precisely integrating the conventional thrombolytic strategy with photothermal therapy. After co-assembly engineering optimization, a fibrin-targeting peptide-decorated nanoassembly of DiR (a photothermal probe) and ticagrelor (TGL, an antiplatelet drug) is prepared for thrombus-homing delivery, abbreviated as FT-DT NPs. The elaborately engineered nanoassembly shows multiple advantages, including simple preparation with high drug co-loading capacity, synchronous delivery of two drugs with long systemic circulation, thrombus-targeted accumulation with self-indicating function, as well as photothermal-potentiated thrombus penetration and thrombolysis with high therapeutic efficacy. As expected, FT-DT NPs not only show bright fluorescence signals in the embolized vessels, but also perform photothermal/antiplatelet synergistic thrombolysis in vivo. This study offers a simple and versatile co-delivery nanoplatform for imaging-guided photothermal/antiplatelet dual-modality thrombolysis.
The development of novel high-resolution
separation techniques is crucial for advancing the complex sample
analysis necessary for high-throughput top-down proteomics. Recently,
our group developed an offline 2D high-pH RPLC/low-pH RPLC separation
method and demonstrated good orthogonality between these two RPLC
formats. Specifically, ultrahigh-pressure long capillary column RPLC
separation has been applied as the second dimensional low-pH RPLC
separation for the improvement of separation resolution. To further
improve the throughput and sensitivity of the offline approach, we
developed an online 2D ultrahigh-pressure nano-LC system for high-pH
and low-pH RPLC separations in top-down proteomics. An online microtrap
column with a dilution setup was used to collect eluted proteins from
the first dimension high-pH separation and inject the fractions for
ultrahigh-pressure long capillary column low-pH RPLC separation in
the second dimension. This automatic platform enables the characterization
of 1000+ intact proteoforms from 5 μg of intact E. coli cell lysate in 10 online-collected fractions. Here, we have demonstrated
that our online 2D pH RP/RPLC system coupled with top-down proteomics
holds the potential for deep proteome characterization of mass-limited
samples because it allows the identification of hundreds of intact
proteoforms from complex biological samples at low microgram sample
amounts.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.