Due to the high morbidity and mortality of cardiovascular diseases, there is an urgent need for research on antithrombotic strategies. In view of the short half-life, insufficient drug penetration, poor targeting capabilities, and hemorrhagic side-effects of traditional thrombus treatment methods, the combination of thrombolytic therapy and nanocarriers brought by the development of nanotechnology in recent years may provide effective solutions for these undesirable side-effects caused by insufficient targeting. Polymeric nanocarriers, based on macromolecules and various functional groups, can connect specific targeting molecules together through chemical modification to achieve the protection and targeted delivery of thrombolytic drugs. However, simple chemical molecular modifications may be easily affected by the physiological environment encountered in the circulatory system. Therefore, the modification of nanocarriers with cell membranes can provide camouflage to these platforms and help to extend their circulation time while also imparting them with the biological functions of cell membranes, thus providing them with precise targeting capabilities, among which the most important is the biological modification of platelet membranes. In addition, some nanoparticles with their own therapeutic functions have also been developed, such as polypyrrole, which can exhibit a photothermal effect to induce thrombolysis. Herein, combined with the mechanism of thrombosis and thrombolysis, we outline the recent advances achieved with thrombus-targeting nanocarriers with regard to thrombosis treatment. On this basis, the design considerations, advantages, and challenges of these thrombolytic therapies in clinical transformation are discussed.
Chemoresistance of cancer cells is conventionally quantified by half-maximal inhibitory concentration (IC 50 ) or multidrug resistance gene 1 (MDR1) values, but these metrics can only reflect the overall drug resistance level of a cancer cell line. Meanwhile, the multidimensional evaluation of both the heterogeneity in a cell line and the drug resistance degree of each cell still presents a daunting challenge. We report here that the cellular heterogeneity, cellular cross contamination, and the proportion of chemoresistant cancer cells can be visualized via flow cytometry through the differential cellular retention of fluorescent ZIF-8 nanoparticles. In addition, we show that the degree of drug resistance exhibited by each cell subpopulation can be quantified by differing fluorescence of the drugresistant and drug-sensitive cells in the corresponding flow cytometry profile, and the quantified metric S is highly consistent with the MDR1 expression results. Importantly, this novel strategy is applicable to various cancer cell lines, thus demonstrating a universal diagnosis platform for multidimensional, quantitative, and highly efficient diagnosis of cancer chemoresistance.
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