The role of lipoproteins in the delivery of tumour-targeting photosensitizers |
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| Institution: | 1. Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, 393 West Binshui Road, Xiqing District, Tianjin 300387, China;2. Tianjin Center for Control and Prevention of Aquatic Animal Infectious Disease, 442 South Jiefang Road, Hexi District, Tianjin 300221, China;1. Institute of Diagnostic and Interventional Radiology, University Hospital Zurich and University of Zurich, CH-8091 Zurich, Switzerland;2. Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-14186, Stockholm, Sweden;3. Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, D-68167, Mannheim, Germany;1. Department of Chemistry and Biochemistry, The University of Arizona, Tucson, AZ 85721, United States;2. College of Pharmacy, University of Oklahoma Health Science Center, Oklahoma City, OK 73117, United States;1. University of Tübingen, Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen, Germany;2. Technische Universität München, M2—Lehrstuhl für Numerische Mathematik, Boltzmannstraße 3, 85748 Garching, Germany;3. Technische Universität München, M6—Lehrstuhl für Mathematische Modellierung, Boltzmannstraße 3, 85748 Garching, Germany;1. Department of General and Inorganic Chemistry, Institute of Chemistry, University of Pannonia, PO Box 158, 8201 Veszprém, Hungary;2. Institute of Physical and Theoretical Chemistry, Graz University of Technology, Stremayrgasse 9, Graz 8010, Austria |
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| Abstract: | - 1.I. Serum lipoproteins play an important role in the in vivo transport of several porphyrinoid derivatives having a moderate or high degree of hydrophobicity.
- 2.2. There appears to exist a correlation between the extent of photosensitizer association with low-density lipoproteins (LDL) and the efficiency of tumour targeting by some classes of photosensitizers, such as differently sulphonated porphyrins and phthalocyanines, haematoporphyrin dialkylethers and unsubstituted phthalocyanines and naphthalocyanines.
- 3.3. In all cases, LDL-carried photosensitizers are preferentially released to malignant cells; hence, direct cell damage appears to be the major determinant of tumour damage consequent to photodynamic therapy.
- 4.4. Present evidence suggests that the LDL-associated photosensitizer is accumulated by tumour cells largely via a receptor-mediated endocytotic process.
- 5.5. Thus, the use of delivery systems for orientating a systemically injected photosensitizer towards lipoproteins has been explored; promising results have been obtained by incorporation of the dye into liposomal vesicles, oil emulsions or inclusion complexes, as well as by precomplexation of the dye with LDL.
- 6.6. Moreover, a suitable choice of the chemical constituents of the delivery system and the experimental conditions allows one to modulate the photosensitizer distribution among the different lipoproteins.
- 7.7. The occurrence of tumour-targeting strategies other than the LDL pathway is briefly discussed.
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