Despite the large number of polymeric nanodelivery systems that have been recently developed, there is still room for improvement in terms of therapeutic efficiency. Most reported nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug leakage with a consequent reduction in efficacy and an increase in systemic toxicity. Herein, we present a strategy for covalent drug conjugation to the nanodevice to overcome this drawback. In particular, we characterize and evaluate an effective therapeutic polymeric PEGylated nanosystem for controlled pH-sensitive drug release on a breast cancer (MDA-MB-231) and two lung cancer (A549 and H520) cell lines. A significant reduction in the required drug dose to reach its half maximal inhibitory concentration (IC50 value) was achieved by conjugation of the drug to the nanoparticles, which leads to an improvement in the therapeutic index by increasing the efficiency. The genotoxic effect of this nanodevice in cancer cells was confirmed by nucleus histone H2AX specific immunostaining. In summary, we successfully characterized and validated a pH responsive therapeutic polymeric nanodevice in vitro for controlled anticancer drug release.
In this manuscript, we report the development of a versatile, robust, and stable targeting nanocarrier for active delivery. This nanocarrier is based on bifunctionalized polymeric nanoparticles conjugated to a monoclonal...
Barcoding and pooling cells for processing as a composite
sample
are critical to minimize technical variability in multiplex technologies.
Fluorescent cell barcoding has been established as a standard method
for multiplexing in flow cytometry analysis. In parallel, mass-tag
barcoding is routinely used to label cells for mass cytometry. Barcode
reagents currently used label intracellular proteins in fixed and
permeabilized cells and, therefore, are not suitable for studies with
live cells in long-term culture prior to analysis. In this study,
we report the development of fluorescent palladium-based hybrid-tag
nanotrackers to barcode live cells for flow and mass cytometry dual-modal
readout. We describe the preparation, physicochemical characterization,
efficiency of cell internalization, and durability of these nanotrackers
in live cells cultured over time. In addition, we demonstrate their
compatibility with standardized cytometry reagents and protocols.
Finally, we validated these nanotrackers for drug response assays
during a long-term coculture experiment with two barcoded cell lines.
This method represents a new and widely applicable advance for fluorescent
and mass-tag barcoding that is independent of protein expression levels
and can be used to label cells before long-term drug studies.
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