Ricchelli F, Jori G, Moreno G, Vinzens F, Salet C
Department of Biology, University of Padova, Italy.
J Photochem Photobiol B. 1990 Jun;6(1-2):69-77. doi: 10.1016/1011-1344(90)85075-8.
The mechanism of the sensitizer-membrane interactions has been studied by following the distribution properties of selected porphyrins, including haematoporphyrin (HP) and protoporphyrin (PP), into unilamellar liposomes of dipalmitoyl phosphatidylcholine (DPPC). The endomembrane distribution of HP and PP has been checked as a function of the membrane fluidity and composition by fluorescence polarization and quenching techniques. At porphyrin concentrations below 0.5 microM, HP and PP exclusively localize in the inner phospholipid monolayer; at higher concentrations, the outer monolayer also becomes populated. The porphyrin binding sites in liposomes, however, are different for HP and PP: HP preferentially distributes into water-accessible lipid regions, while PP localizes in the most hydrophobic loci of the lipid matrix. A porphyrin redistribution occurs when the fluidity properties of the liposomes are changed by addition of cholesterol or cardiolipin. In DPPC-cholesterol vesicles, all HP molecules dissolve in DPPC-rich regions while all PP molecules partition in cholesterol-rich environments. In DPPC-cardiolipin vesicles both porphyrins preferentially localize in regions accessible to the external medium. The effect of the nature of the carrier on porphyrin distribution in membranes has been studied by following the uptake and photosensitization properties of free and DPPC-incorporated PP and HP with rat liver mitochondria. The porphyrin photosensitizing efficiency has been checked by following the impairment of the respiratory function of mitochondria upon irradiation. Liposome-bound HP is less active than aqueous HP in determining membrane photodamage in mitochondria. On the contrary, aqueous PP is a very poor sensitizer as compared to a DPPC liposome-entrapped drug.(ABSTRACT TRUNCATED AT 250 WORDS)
通过追踪选定卟啉（包括血卟啉（HP）和原卟啉（PP））在二棕榈酰磷脂酰胆碱（DPPC）单层脂质体中的分布特性，研究了敏化剂与膜的相互作用机制。通过荧光偏振和猝灭技术，检测了HP和PP在膜内的分布与膜流动性和组成的关系。在卟啉浓度低于0.5微摩尔时，HP和PP仅定位于内层磷脂单分子层；在较高浓度时，外层单分子层也有分布。然而，脂质体中HP和PP的卟啉结合位点不同：HP优先分布于可接触水的脂质区域，而PP定位于脂质基质中最疏水的位点。当通过添加胆固醇或心磷脂改变脂质体的流动性时，会发生卟啉重新分布。在DPPC - 胆固醇囊泡中，所有HP分子溶解在富含DPPC的区域，而所有PP分子分配到富含胆固醇的环境中。在DPPC - 心磷脂囊泡中，两种卟啉都优先定位于外部介质可接触的区域。通过追踪游离的和DPPC包裹的PP和HP与大鼠肝线粒体的摄取和光敏化特性，研究了载体性质对卟啉在膜中分布的影响。通过照射后线粒体呼吸功能的损伤来检测卟啉的光敏化效率。在导致线粒体膜光损伤方面，脂质体结合的HP比水性HP活性低。相反，与DPPC脂质体包裹的药物相比，水性PP是一种非常差的敏化剂。（摘要截断于250字）
