3 research outputs found
TCAg1 supplementary information from A reversible fluorescent probe for monitoring Ag(I) ions
Supplementary figure
A Coumarin-Based Array for the Discrimination of Amyloids
Self-assembly
of misfolded proteins can lead to the formation of
amyloids, which are implicated in the onset of many pathologies including
Alzheimer’s disease and Parkinson’s disease. The facile
detection and discrimination of different amyloids are crucial for
early diagnosis of amyloid-related pathologies. Here, we report the
development of a fluorescent coumarin-based two-sensor array that
is able to correctly discriminate between four different amyloids
implicated in amyloid-related pathologies with 100% classification.
The array was also applied to mouse models of Alzheimer’s disease
and was able to discriminate between samples from mice corresponding
to early (6 months) and advanced (12 months) stages of Alzheimer’s
disease. Finally, the flexibility of the array was assessed by expanding
the analytes to include functional amyloids. The same two-sensor array
was able to correctly discriminate between eight different disease-associated
and functional amyloids with 100% classification
Hypoxia-Responsive Cobalt Complexes in Tumor Spheroids: Laser Ablation Inductively Coupled Plasma Mass Spectrometry and Magnetic Resonance Imaging Studies
Dense tumors are
resistant to conventional chemotherapies due to the unique tumor microenvironment
characterized by hypoxic regions that promote cellular dormancy. Bioreductive
drugs that are activated in response to this hypoxic environment are
an attractive strategy for therapy with anticipated lower harmful
side effects in normoxic healthy tissue. Cobalt bioreductive pro-drugs
that selectively release toxic payloads upon reduction in hypoxic
cells have shown great promise as anticancer agents. However, the
bioreductive response in the tumor microenvironment must be better
understood, as current techniques for monitoring bioreduction to Co(II)
such as X-ray absorption near-edge structure and extended X-ray absorption
fine structure provide limited information on speciation and require
synchrotron radiation sources. Here, we present magnetic resonance
imaging (MRI) as an accessible and powerful technique to monitor bioreduction
by treating the cobalt complex as an MRI contrast agent and monitoring
the change in water signal induced by reduction from diamagnetic Co(III)
to paramagnetic Co(II). Cobalt pro-drugs built upon the tris(2-pyridylmethyl)amine
ligand scaffold with varying charge were investigated for distribution
and activity in a 3D tumor spheroid model by laser ablation inductively
coupled plasma mass spectrometry (LA-ICP-MS) and MRI. In addition,
paramagnetic <sup>1</sup>H NMR spectroscopy of spheroids enabled determination
of the speciation of activated Co(II)TPAx complexes. This study demonstrates
the utility of MRI and associated spectroscopy techniques for understanding
bioreductive cobalt pro-drugs in the tumor microenvironment and has
broader implications for monitoring paramagnetic metal-based therapies