18 research outputs found
Retargeting Polyomavirus-Like Particles to Cancer Cells by Chemical Modification of Capsid Surface
Virus-like particles
based on polyomaviruses (PVLPs) are promising
delivery devices for various cargoes, including nucleic acids, imaging
probes, and therapeutic agents. In biological environments, the major
coat protein VP1 interacts with ubiquitously distributed sialic acid
residues, and therefore PVLPs show a broad tropism. For selective
targeting, appropriate engineering of the PVLP surface is needed.
Here, we describe a chemical approach to retarget PVLPs to cancer
cells displaying abnormally high levels of transferrin receptor. We
created an array of transferrin molecules on the surface of PVLPs
by combining a high-yielding bioconjugation approach with specific
point modification of transferrin. This artificial surface protein
architecture enables (i) suppression of natural VP1-specific interactions
by blocking the surface conformational epitope on the VP1 protein,
(ii) unusually high cellular uptake efficiency, and (iii) selective
retargeting of PVLPs to osteosarcoma (U2OS) and lymphoblastoid leukemia
(CCRF-CEM) cells
Supported Lipid Bilayers on Fluorescent Nanodiamonds: A Structurally Defined and Versatile Coating for Bioapplications
International audienc
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 polyÂ(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