Dual use of porphyrazines as sensitizers and viscosity markers in photodynamic therapy

Abstract

Porphyrazines have recently emerged as a useful class of tetrapyrroles suitable for photodynamic therapy of cancer (PDT) with excellent uptake and retention properties in vivo. Here we demonstrate that the photophysical properties of cyano -phenyl porphyrazine pz1 are strongly viscosity dependent, i.e. the fluorescence lifetime and the quantum yield of pz1 increase as a function of solution viscosity. We have calibrated pz1 as a red-emitting fluorescent 'molecular rotor' in a large range of viscosities from 80 to ca 5500 cP, in solutions of various solvent compositions and temperature. On the other hand, pz1 works as an efficient PDT sensitiser, i.e. it induces apoptosis and necrosis in cells upon irradiation with red light through formation of singlet oxygen. We demonstrate that PDT in cells using pz1 is accompanied by a significant viscosity increase by monitoring the fluorescence lifetime of the rotor. We suggest that this increase could be used as a completely new type of diagnostic and dosimetry tool during a PDT treatment.

Cyano-Aryl Porphyrazine Pigments with Polycyclic Substituents as the Promising Agents for Photodynamic Therapy and Potential Sensors of Local Viscosity

“…To estimate the capacities of the new cyano-aryl porphyrazine pigment PzIV containing peripheral 9-phenanthrenyl substituents we have investigated the photophysical properties (Table 1) and quantified its dark and photoinduced cytotoxicity to compare them with the same characteristics for relate porphyrazines pzI-pzIII. [11,13] Absorption spectra of cyano-aryl porphyrazines pzI-pzIV are typical for non-associated porphyrazine macrocycles (Figure 2A). But the noticeable shift of Q-band to longer wavelengths due to aryl substituent aromatic system extension (particularly, for pzIV) had beеn observed.…”

“…Our recent papers [11,13,20] presented the photophysical proofs that the cyano-aryl porphyrazine tetrapyrrol dyes pzI, pzII and pzIII were in fact fluorescent molecular rotors that could be potentially utilized to determine the local intracellular viscosity even under conditions of its dynamic change, for example, under the conditions of photodynamic therapy. Similarly, we found the significant dependence of the fluorescence intensity of pzIV on the medium viscosity ( Figure 7A).…”

“…We have found that the structure of peripheral aryl groups coupled with macrocycle core significantly affects photophysical and cytotoxic properties of porphyrazines. [11][12][13] So, the porphyrazine peripheral framing variation can be used as an effective tool for a therapeutic potential fine tuning.…”

Photocontrollable release and enhancement of photodynamic therapy based on host–guest supramolecular amphiphiles

“…[13][14][15][16][17][18][19][20] The light irradiated PSs (with different doses, times and locations) could make the PDT more controllable and minimally invasive. [28][29][30][31][32][33] Traditional anticancer drugs based on chemotherapy easily show toxicity both in tumour cells and normal cells during cancer therapy. For example, porfimer sodium (Photofrin), verteporfrin (Visudyne) and 5-aminolevulinic acid (Levulan) are approved by Food and Drug Administration (FDA), and meta-tetrahydroxyphenyl chlorin (mTHPC, Foscan) is approved by EU in 2001.…”

A lifetime in photochemistry; some ultrafast measurements on singlet states

“…In a recent report, Kuimova et al [77] used a porphyrazine as both a sensitizer and viscosity marker in cells undergoing PDT. Aggregation is a problem with many if not most sensitizers based upon porphyrin and porphyrin-like compounds such as phthalocyanines and porphyrazines.…”