Laboratory of Biomedical Optics and Applied Biophysics, School of Electrical and Computer Engineering, National Technical University of Athens, Iroon Politechniou 9, Zografou Campus, 157 80 Athens, Greece.
Photodiagnosis Photodyn Ther. 2012 Dec;9(4):344-54. doi: 10.1016/j.pdpdt.2012.03.008. Epub 2012 May 3.
m-THPC (Foscan(®)) is one of the most potent second generation photosensitizers used in photodynamic therapy, photoactivated at higher wavelengths (652 nm). However, its strongly hydrophobic nature causes aggregation of the molecules and prevents its unbiased bioavailability in the biological media, resulting in lower accumulation in the tumor cells. Several strategies have been adopted to improve the photodynamic characteristics of the photosensitizer. Among them, very promising seems to be the encapsulation of the molecule into liposomes, due to the superior properties of liposomes as drug carriers.
In this paper the photodynamic characteristics of the PEGylated liposomal formulation of m-THPC, Fospeg, using the human prostate cancer cell line LNCaP, as an in vitro model, were investigated. In addition the spectral characteristics, cellular uptake and localization, dark and light induced cytotoxicity and photodynamic efficacy of Foscan(®) and Fospeg were compared.
Fospeg, compared with Foscan, showed higher intracellular uptake at any concentration and incubation time. Regarding PDT efficacy, Fospeg produced more severe cytotoxicity than Foscan(®) at any concentration and energy dose. Using Fospeg, the lowest concentration (0.22 μM) and energy dose (180 mJ/cm(2)) was adequate to result in the death of 50% of the cells 24h post PDT while an approximately 10 times higher Foscan(®) concentration (1.8 μM) was needed to result in the same cytotoxicity.
The use of the PEGylated liposomal formulation of m-THPC resulted in the improvement of its intracellular uptake and the enhancement of its photodynamic activity. Fospeg, compared to Foscan(®), proved to be a more advantageous photosensitizer for photodynamic therapy.
m-THPC（Foscan(®)）是第二代用于光动力疗法的最有效的光敏剂之一，在较高波长（652nm）下被光激活。然而，其强烈的疏水性导致分子聚集，阻止其在生物介质中无偏的生物利用度，从而导致肿瘤细胞中的积累减少。已经采用了几种策略来改善光敏剂的光动力特性。其中，将分子包封在脂质体中似乎是一种很有前途的策略，因为脂质体作为药物载体具有优越的性能。
本文研究了 m-THPC 的 PEG 化脂质体制剂 Fospeg 在人前列腺癌细胞系 LNCaP 中的光动力特性，作为体外模型。此外，还比较了 Foscan(®)和 Fospeg 的光谱特性、细胞摄取和定位、暗毒性和光毒性以及光动力疗效。
与 Foscan 相比，Fospeg 在任何浓度和孵育时间下都显示出更高的细胞内摄取。关于 PDT 疗效，Fospeg 在任何浓度和能量剂量下都比 Foscan(®)产生更严重的细胞毒性。使用 Fospeg，最低浓度（0.22μM）和能量剂量（180mJ/cm(2)）足以在 PDT 后 24 小时导致 50%的细胞死亡，而大约需要 10 倍更高的 Foscan(®)浓度（1.8μM）才能产生相同的细胞毒性。
使用 m-THPC 的 PEG 化脂质体制剂可提高其细胞内摄取并增强其光动力活性。与 Foscan(®)相比，Fospeg 被证明是一种更有利的光动力治疗光敏剂。
