Porphyrin‐related photosensitizers for cancer imaging and therapeutic applications

Abstract

SummaryA photosensitizer is defined as a chemical entity, which upon absorption of light induces a chemical or physical alteration of another chemical entity. Some photosensitizers are utilized therapeutically such as in photodynamic therapy (PDT) and for diagnosis of cancer (fluorescence diagnosis, FD). PDT is approved for several cancer indications and FD has recently been approved for diagnosis of bladder cancer. The photosensitizers used are in most cases based on the porphyrin structure. These photosensitizers generally accumulate in cancer tissues to a higher extent than in the surrounding tissues and their fluorescing properties may be utilized for cancer detection. The photosensitizers may be chemically synthesized or induced endogenously by an intermediate in heme synthesis, 5-aminolevulinic acid (5-ALA) or 5-ALA esters. The therapeutic effect is based on the formation of reactive oxygen species (ROS) upon activation of the photosensitizer by light. Singlet oxygen is assumed to be the most important ROS for the therapeutic outcome. The fluorescing properties of the photosenisitizers can be used to evaluate their intracellular localization and treatment effects. Some photosensitizers localize intracellularly in endocytic vesicles and upon light exposure induce a release of the contents of these vesicles, including externally added macromolecules, into the cytosol. This is the basis for a novel method for macromolecule activation, named photochemical internalization (PCI). PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins, immunotoxins, gene-encoding plasmids, adenovirus, peptide-nucleic acids and the chemotherapeutic drug bleomycin. The background and present status of PDT, FD and PCI are reviewed.

In Vivo Photoactivation Without “Light”: Use of Cherenkov Radiation to Overcome the Penetration Limit of Light

“…Most photosensitizers of photodynamic therapy have to be activated using light in the nearinfrared range [1][2][3]. However, porphyrin compounds, the drugs that are most commonly used in photodynamic therapy, exhibit stronger absorption and excitation in the range of 400-600 nm [22][23][24]. Radiation luminescence could be used to excite molecules for photodynamic therapy in this higher energy portion of the spectrum.…”

Nanodrug applications in photodynamic therapy

“…Here photochemical internalization, i.e. the light triggered release of the active drug into the cytosol can offer potential improvements [87].…”

Site-directed photoproteolysis of 8-oxoguanine DNA glycosylase 1 (OGG1) by specific porphyrin-protein probe conjugates: A strategy to improve the effectiveness of photodynamic therapy for cancer

“…ROS-induced cell damage in general and oxidatively damaged DNA in particular are thought to be the main reasons for malignant cell death and tumor ablation after PDT [1,2,28,45]. Since the mOGG1 protein was successfully photolyzed by porphyrin-conjugated antibodies or porphyrin-conjugated streptavidin when irradiated with wavelengths commonly used for PDT, the success of this strategy opens the possibility of using porphyrin-conjugated probes to improve site-directed PDT both by in situ producing ROS in tumor cells and site-directing part of the photochemical reaction to obliterate an important DNA repair enzyme, OGG1.…”

“…PDT in cancer therapy is based on the observation that certain non-toxic photosensitizer (PS) molecules, of which the most prominent is Photofrin, have a tendency to accumulate preferentially in malignant cells [1,2]. Although most PS molecules with potential applicability for PDT are still in the research phase, PS structurally share the tetrapyrrole nucleus and include porphyrins, chlorins, bacteriochlorins, phthalocyanines and texaphyrins [3].…”