We report the design of a water-soluble, quaternized tamoxifen photoprobe and demonstrate its application for light-controlled induction of green fluorescent protein expression via a Cre-ER recombinase system.
Riboflavin receptors are overexpressed
in malignant cells from
certain human breast and prostate cancers, and they constitute a group
of potential surface markers important for cancer targeted delivery
of therapeutic agents and imaging molecules. Here we report on the
fabrication and atomic force microscopy (AFM) characterization of
a core–shell nanocomposite consisting of a gold nanoparticle
(AuNP) coated with riboflavin receptor-targeting poly(amido amine)
dendrimer. We designed this nanocomposite for potential applications
such as a cancer targeted imaging material based on its surface plasmon
resonance properties conferred by AuNP. We employed AFM as a technique
for probing the binding interaction between the nanocomposite and
riboflavin binding protein (RfBP) in solution. AFM enabled precise
measurement of the AuNP height distribution before (13.5 nm) and after
chemisorption of riboflavin-conjugated dendrimer (AuNP–dendrimer;
20.5 nm). Binding of RfBP to the AuNP–dendrimer caused a height
increase to 26.7 nm, which decreased to 22.8 nm when coincubated with
riboflavin as a competitive ligand, supporting interaction of AuNP–dendrimer
and its target protein. In summary, physical determination of size
distribution by AFM imaging can serve as a quantitative approach to
monitor and characterize the nanoscale interaction between a dendrimer-covered
AuNP and target protein molecules in vitro.
Design of cancer-targeting nanotherapeutics relies on a pair of two functionally orthogonal molecules, one serving as a cancer cell-specific targeting ligand, and the other as a therapeutic cytotoxic agent. The present study investigates the validity of an alternative simplified strategy where a dual-acting molecule which bears both targeting and cytotoxic activity is conjugated to the nanoparticle as cancer-targeting nanotherapeutics. Herein we demonstrate that methotrexate is applicable for this dual-acting strategy due to its reasonable affinity to folic acid receptor (FAR) as a tumor biomarker, and cytotoxic inhibitory activity of cytosolic dihydrofolate reductase. This article describes design of new methotrexate-conjugated poly(amidoamine) (PAMAM) dendrimers, each carrying multiple copies of methotrexate attached through a stable amide linker. We evaluated their dual biological activities by performing surface plasmon resonance spectroscopy, a cell-free enzyme assay and cell-based experiments in FAR-overexpressing cells. This study identifies the combination of an optimal linker framework and multivalency as the two key design elements that contribute to achieving potent dual activity.
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