4 research outputs found
Like a bolt from the blue : phthalocyanines in biomedical optics
The purpose of this review is to compile preclinical and clinical results on phthalocyanines (Pcs) as photosensitizers (PS) for Photodynamic Therapy (PDT) and contrast agents for fluorescence imaging. Indeed, Pcs are excellent candidates in these fields due to their strong absorbance in the NIR region and high chemical and photo-stability. In particular, this is mostly relevant for their in vivo activation in deeper tissular regions. However, most Pcs present two major limitations, i.e., a strong tendency to aggregate and a low water-solubility. In order to overcome these issues, both chemical tuning and pharmaceutical formulation combined with tumor targeting strategies were applied. These aspects will be developed in this review for the most extensively studied Pcs during the last 25 years, i.e., aluminium-, zinc- and silicon-based Pcs
Optimization of proteolytically induced photosensitizers for fluorescence imaging and Photodynamic Therapy
The scope of this thesis is to investigate and improve efficiency and selectivity of Photodetection and Photodynamic Therapy using near-infrared photosensitizers (PS) and protease sensitive photosensitizer prodrugs (PSPP) for PS-controlled, versatile and modulable delivery to diseased tissues. Photosensitizers comprising of phthalocyanines, and pheophorbide-a and PSPP Constructs i.e. Molecular Beacons, Protease Sensitive Polymeric Prodrugs (PPP) and Regioselectively Addressable Functionalized Templates (RAFT) Protease Sensitive Prodrugs were successfully synthesized and evaluated both in vitro and in vivo. 50% of prostate cancer (PC-3) cell death was achieved for PS-doses as low as 100nM for a light dose of 10J/cm2 using RAFT prodrugs. Complete tumor eradication was observed on 3 out of 7 mice bearing tumor xenografts using PPP. The PSPP therefore exhibited very promising potential for detection, imaging and treatment of the tumors. Having established the modulability of the prodrug approaches, new therapeutical applications could be envisaged in diseases associated with proteases up-regulated levels
Kondrat'eva ligation: Diels-Alder-based irreversible reaction for bioconjugation
International audienceDiversification of existing chemoselective ligations is required to efficiently access complex and well-defined biomolecular assemblies with unique and valuable properties. The development and bioconjugation applications of a novel Diels-Alder-based irreversible site-specific ligation are reported. The strategy is based on a Kondrat'eva cycloaddition between bioinert and readily functionalizable 5-alkoxyoxazoles and maleimides that readily react together under mild and easily tunable reaction conditions to afford a fully stable pyridine scaffold. The potential of this novel bioconjugation is demonstrated through the preparation of fluorescent conjugates of biomolecules and a novel Förster resonance energy transfer (FRET)-based probe suitable for the in vivo detection and imaging of urokinase-like plasminogen activator (uPA), which is a key protease involved in cancer invasion and metastasis
Kondratâeva Ligation: DielsâAlder-Based Irreversible Reaction for Bioconjugation
Diversification of existing chemoselective
ligations is required
to efficiently access complex and well-defined biomolecular assemblies
with unique and valuable properties. The development and bioconjugation
applications of a novel DielsâAlder-based irreversible site-specific
ligation are reported. The strategy is based on a Kondratâeva
cycloaddition between bioinert and readily functionalizable 5-alkoxyoxazoles
and maleimides that readily react together under mild and easily tunable
reaction conditions to afford a fully stable pyridine scaffold. The
potential of this novel bioconjugation is demonstrated through the
preparation of fluorescent conjugates of biomolecules and a novel
FoÌrster resonance energy transfer (FRET)-based probe suitable
for the in vivo detection and imaging of urokinase-like plasminogen
activator (uPA), which is a key protease involved in cancer invasion
and metastasis