4 research outputs found
Inhibitor–GCPII Interaction: Selective and Robust System for Targeting Cancer Cells with Structurally Diverse Nanoparticles
Glutamate carboxypeptidase II (GCPII)
is a membrane protease overexpressed
by prostate cancer cells and detected in the neovasculature of most
solid tumors. Targeting GCPII with inhibitor-bearing nanoparticles
can enable recognition, imaging, and delivery of treatments to cancer
cells. Compared to methods based on antibodies and other large biomolecules,
inhibitor-mediated targeting benefits from the low molecular weight
of the inhibitor molecules, which are typically stable, easy-to-handle,
and able to bind the enzyme with very high affinity. Although GCPII
is established as a molecular target, comparing previously reported
results is difficult due to the different methodological approaches
used. In this work, we investigate the robustness and limitations
of GCPII targeting with a diverse range of inhibitor-bearing nanoparticles
(various structures, sizes, bionanointerfaces, conjugation chemistry,
and surface densities of attached inhibitors). Polymer-coated nanodiamonds,
virus-like particles based on bacteriophage Qβ and mouse polyomavirus,
and polymeric poly(HPMA) nanoparticles with inhibitors attached by
different means were synthesized and characterized. We evaluated their
ability to bind GCPII and interact with cancer cells using surface
plasmon resonance, inhibition assay, flow cytometry, and confocal
microscopy. Regardless of the diversity of the investigated nanosystems,
they all strongly interact with GCPII (most with low picomolar <i>K</i><sub>i</sub> values) and effectively target GCPII-expressing
cells. The robustness of this approach was limited only by the quality
of the nanoparticle bionanointerface, which must be properly designed
by adding a sufficient density of hydrophilic protective polymers.
We conclude that the targeting of cancer cells overexpressing GCPII
is a viable approach transferable to a broad diversity of nanosystems
Misligholdsbeføyelser ved aksjonæravtaler
Characteristics of the 16 SSR markers used in this study with indication of the corresponding multiplex and dye. Footnotes: a [61]; b [60]; c [59]; d [62]; e Primer concentration within a given multiplex has been adjusted to get more homogeneous SSR marker amplification intensities. (XLSX 10 kb