In Vivo and In Vitro Photodynamic Studies with Benzochlorin Iminium Salts Delivered by a Lipid Emulsion

Abstract

Benzochlorin iminium salts (BIs) are hydrophobic photosensitizers based on an octaethylbenzochlorin nucleus that absorb in the near-IR region of the visible spectrum. In these studies the photodynamic activities of the zinc, copper and metal-free BI derivatives were compared in vivo in C3H-HeJ mice bearing a mammary adenocarcinoma tumor line. In vitro studies were also performed with the radiation-induced fibrosarcoma tumor line. An argon-pumped Ti-sapphire laser tuned to deliver light between 710 and 800 nm or an Oriel arc-lamp filtered to deliver broadband light above 590 nm were used as light source. A lipid emulsion was used as the delivery system for sensitizers in all studies. A pronounced solvent dependence was observed for the Q band for each of all iminium salts examined. As an example, the metal-free (BI) derivative had an absorption maximum at 798 nm in dichloromethane and at 727 nm in serum. The action spectra showed a greater PDT response at blue-shifted wavelengths for each of the three iminium salts both in vivo and in vitro. Among the three derivatives, the zinc analog (ZnBI) produced the greatest tumor regression at the low drug/light dose of 0.7 (mumole/kg and 200 J/cm2. These results indicate that iminium salts have characteristics that may make them promising third-generation photosensitizers.

Photodynamic Therapy and the Development of Metal-Based Photosensitisers

“…Despite an undetectable triplet state, it appears to be more photoactive towards leukemia cells in vitro and a rat bladder tumour model [106–108]. Suggestions for this unusual effect have pointed to interactions between the cationic iminium group and biomolecules [109]. Such interactions may allow electron-transfer reactions to take place via the short-lived excited singlet state and lead to the formation of radicals and radical ions.…”

“…The copper-free derivative exhibited a tumour response with short intervals between drug administration and photodynamic therapy. Increased in vivo activity was observed with the zinc benzochlorin analogue [109]. …”

Metal Chelation Modulates Phototherapeutic Properties of Mitoxantrone-Loaded Porphyrin–Phospholipid Liposomes

“…33–39 These include altering the cellular uptake, adding contrast agent functionality, or altering the photoactivity and efficacy. 40–42 …”

Synthesis of meso-substituted cationic porphyrins as potential photodynamic agents

“…6 Cationic porphyrins have several interesting features, which make these compounds attractive photosensitizers for a variety of biological systems. [7][8][9][10][11] These porphyrins are able to interact with DNA bases, inducing DNA lesions upon photoactivation. 12,13 Recently, cationic porphyrins have also shown important applications as sensitizers to photoinduce direct inactivation of multidrug resistant microorganisms.…”