Due to the ongoing development of clinical photodynamic therapy (PDT), the search continues for optimized photosensitizers that can overcome some of the side effects associated with this type of treatment modality. The main protagonists being: post-treatment photosensitivity, due to only limited cellular selectivity and post-treatment tumor regrowth, due to the up-regulation of pro-inflammatory agents within the tumor microenvironment. A photosensitizer that could overcome one or both of these drawbacks would be highly attractive to those engaged in clinical PDT. Certain non-steroidal anti-inflammatory drugs (NSAIDs) when used in combination with PDT have shown to increase the cytotoxicity of the treatment modality by targeting the tumor microenvironment. Temoporfin (m-THPC), the gold standard chlorin-based photosensitizer (PS) since its discovery in the 1980’s, has successfully been conjugated to non-steroidal anti-inflammatory compounds, in an attempt to address the issue of post-treatment tumor regrowth. Using a modified Steglich esterification reaction, a library of “iPorphyrins” was successfully synthesized and evaluated for their PDT efficacy.
Rational building strategies and appropriate synthons have been developed for the use of triptycene as a rigid presenting scaffold. Palladium catalyzed cross-coupling reactions such as, Sonogashira and Suzuki couplings were used to install a variety of different synthetic handles around the triptycene periphery in a high yielding and controlled manner. These triptycene molecular handles were investigated for their potential in the construction of molecular arrays with defined spatial orientation e.g., for host-guest interactions or drug delivery systems. Such molecular synthons afforded expansion from the triptycene core employing arm extension increasing the internal free volume characteristic of triptycene scaffolds for such applications. In addition a range of mesogenic and glycosyl triptycene derivatives were achieved as a synthetic proof of concept for future work on potential drug delivery systems.
We examine here a series of meso-phenyl porphyrin micro- and nanostructures. Optical absorption and emission spectroscopy imaging and atomic force microscopy are used to investigate the effect of peripheral groups in nano- and microstructures of 5,10,15,20-tetraphenylporphyrin (H2TPP) compared to three other phenylporphyrins, i.e. 5,10,15-triphenylporphyrin (H2-Tri-PP), 5,10-diphenylporphyrin (H25,10-BPP) and 5,15-diphenylporphyrin (H25,15-BPP) molecules. We show that nanospheres and nanorods are formed, the occurrence and properties of which are influenced by the number and position of the phenyl substituents.
Porphyrins and chlorins such as Foscan® have a natural proclivity to accumulate in cancer cells. This trait has made them good candidates for photosensitizers and as imaging agents in phototherapy. In order to improve on cellular selectivity to lower post-treatment photosensitivity bile acid porphyrin bioconjugates have been prepared and investigated in esophageal cancer cells. Bile acids which are known to selectively bind to, or be readily taken up by cancer cells were chosen as targeting moieties. Synthesis of the conjugates was achieved via selective nucleophilic monofunctionalization of 5,10,15,20-tetrahydroxyphenylporphyrins with propargyl bromide followed by Cu(I) mediated cycloaddition with bile acid azides in good yields. The compounds were readily taken up by esophageal cancer cells but showed no PDT activity.
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