Liposome‐Mediated Delivery of Photosensitizers: Localization of Zinc (11)‐Phthalocyanine within Implanted Tumors after Intravenous Administration

Abstract

CGP55847, liposomal zinc(II)-phthalocyanine (Zn-Pc), was administered by the intravenous route to Swiss mice bearing intramuscularly implanted Ehrlich carcinomas or to C57/BL6 mice bearing subcutaneously implanted B16 melanomas. Tumors were removed 3 h or 24 h after dosing the intratumoral distribution determined by fluorescence microscopy. Localization of the photosensitizer occurred more rapidly in the Ehrlich carcinoma than in the B16 melanoma; this difference in photosensitizer uptake may be related to a higher degree of vascularization of the carcinoma. The photosensitizer was found in association with blood vessels at 3 h but not 24 h after dosing and appeared to have a greater affinity for areas of tissue necrosis within the tumor compared to viable tumor tissue. Little or no Zn-Pc was detected in the muscle tissue invaded by the Ehrlich carcinoma and was associated with the membranes and the cytosol, but not the nucleus, of cells in both tumors.

Spatial Laser Induced Fluorescence Imaging (SLIFIMG) Analysis to Assess Tissue Photosensitizer Uptake

“…administered photosensitizer by tumor tissue is one of several fundamental determinants of the clinical effectiveness of PDT as mentioned by Weersink, R. A., et al, 1997, Chen, Q., et al., 1996, Love, W. G., et al, 1996 and Windahl, T., et al, 1993 which comply with our obtained results that study of PS tissue uptake reflects many aspects that facilitate the understanding and how we can optimally benefit from this useful treatment modality [17][18][19][20]. Using Matlab to study and analyze tissue auto fluorescence was applied by Kamath SD and Mahato KK 2007 the demonstrated that Matlab is a good tool for the spectral analysis and classification for discrimination of autofluorescence spectra of pathologically certified normal, premalignant, and malignant oral tissues [21]. Korbelik, M. 1993, stated that the most sensitive means of monitoring photosensitizer photodegradation is fluorescence detection and it is therefore important as far as possible to study photodegradation of photosensitizer in tumour tissues under treatment with PDT compared to normal tissues so that a cleaner correlation between photodegradation (fluorescence decreasing) and photodamage may be made [22].…”

Mechanisms of porphyrinoid localization in tumors

“…The highly hydrophobic Zn(II)phthalocyanine (ZnPc, 12) has been selectively delivered in DPPC liposomes to MS-2 fibrosarcoma tumors in mice [117], and a formulation of 131 Ilabelled ZnPc in DPPC liposomes has been shown to be an effective radiodiagnostic agent for this tumor [118]. The specificity of tumor-targeting by ZnPc (12) was further increased using cholesterolenriched DPPC liposomes (up to 20 mol %) [119,120], and liposomes containing palmitoyloleoylph osphatidylcholine and dioleoylphosphatidylserine (POPC/OOPS) [121,122]. The distribution of ZnPc (12) among lipoproteins is dependent upon the nature of the liposome vehicle, in particular its composition and physical state at 37 o C (fluid, gel or quasi-solid); both a fluid state and the presence of cholesterol in the liposome bilayer favor the interaction and binding of ZnPc to LDL and cell membranes [120,121].…”

Quantification of Photocyanine in Human Serum by High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Its Application in a Pharmacokinetic Study

“…In comparing this method with the analytical methods reported previously [14, 18], the present method proved superior with respect to higher simplicity of sample preparation, higher selectivity and sensitivity, and shorter chromatographic analysis time. The present description is the first to utilize the HPLC-MS/MS method for the pharmacokinetic study of photocyanine given by injection to cancer patients.…”

“…Phthalocyanines and their derivatives are also widely used photosensitizers for the PDT of cancer, displaying high absorption of visible light, mainly in the phototherapeutic wavelength window (600–800 nm) [9, 10]. Photosense, Pc4, and CGP55847 are second-generation photosensitizers that have been used in clinical practice [11–14]. …”