Universiteit Leiden

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Proefschrift

Molecular sensors for calcium ion detection via triplet-triplet annihilation upconversion

Cardiovascular diseases (CVDs) are the leading global cause of mortality. Endothelial dysfunction, an early reversible stage of CVD development, is marked by decreased nitric oxide production linked to Ca2+ influx in endothelial cells.

Auteur
V.D. Andreeva
Datum
19 september 2024
Links
Thesis in Leiden Repository

Existing probes for Ca2+ detection application for imaging in tissues is limited by light penetration and autofluorescence. Here, we demonstrate calcium-sensitive systems utilizing triplet-triplet annihilation upconversion (TTA-UC) for intracellular imaging applications. First, we developed a system combining TTA-UC and photoelectron transfer (PET) mechanisms by covalently binding a perylene annihilator with calcium-sensitive moiety. When integrated with a red-light photosensitizer in methanol, the system achieves upconverted blue luminescence only in the presence of Ca2+. For calcium sensing in water, we encapsulated the system in different liposomes and investigated how the lipid composition affects the system sensitivity. Additionally, we studied structure-activity relationships by comparing three modified perylene analogues with varied linkers in homogeneous solution and on liposome. While the sensing properties of the annihilators varied significantly in solutions, the calcium-dependent behavior of the upconverting liposomes correlated mainly with the lipid bilayer composition. This study underscores the necessity of understanding sensor behavior across diverse chemical contexts to advance TTA-UC-based sensing technology for imaging applications.

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