Experimental photodynamic therapy with meso-tetrakisphenylporphyrin (TPP) in liposomes leads to disintegration of human amelanotic melanoma implanted to nude mice
Experimental photodynamic therapy with meso-tetrakisphenylporphyrin (TPP) in liposomes leads to disintegration of human amelanotic melanoma implanted to nude mice
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DOI：
10.1002/ijc.10857
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发表时间：
2003-02-20
影响因子：
6.4
通讯作者：
Klepácek, N
中科院分区：
文献类型：
--
作者：
Jezek, P;Nekvasil, M;Klepácek, N
研究了中四聚苯基卟啉（TPP）脂质体光动力治疗裸鼠无色素黑素瘤的效果。在瘤内施用TPP (15 mg（.)kg(-1)）后，再加上PDT灯照射（600-700 nm，峰值635 nm），肿瘤在PDT后第23天仍保持原来的体积，而对照组的体积增加了6倍。PDT与静脉（i.v）给药脂质体(3.2 mg(.)kg(-1)) TPP大多数分解肿瘤至零体积。黑色素瘤的缓解伴随着肿瘤表面的坏死，并通过细胞核非增生的非变性细胞的出现来记录。肿瘤缓解期毛细血管的空间排列与周围健康组织相同。较低的TPP剂量(1,0.3和0。1 mg.kg(-1))比亲水性TPPS4 (3.2 mg（.)kg(-1)，即磺化TPP）更有效或同样有效，也在脂质体中静脉注射。脂质体TPPS4仅延缓了随后肿瘤生长的发生。商业Photosan 3仅在大约剂量下分解肿瘤。7.5毫克(.)公斤(1);在较低剂量下，它的效果不如TPPS4。第二个PDT周期(3.2 mg(.)kg(-1) TPP或7.5 mg(.)kg(-1) Photosan 3)，在少数未成功治愈的小鼠中进行，主要再次导致肿瘤缓解。由于测量的TPP和TPPS4在黑色素瘤中的含量相似，这些结果表明PDT与TPP等疏水光敏剂的优势。TPP和TPPS4的光物理性质相同，但我们的研究表明，TPP可能具有更有利的细胞内分布，从而导致更有效的PDT。因此，脂质体TPP被认为是一种潜在的合适有效的PDT制剂。(C) 2002 Wiley-Liss, Inc。
Liposomal meso-tetrakis-phenylporphyrin (TPP) was tested for photodynamic therapy (PDT) of human amelanotic melanomas implanted in nude mice. After intratumoural TPP application (15 mg(.)kg(-1)) followed by PDT lamp irradiation (600-700 nm, 635 nm peak), tumours retained their original volume up to the 23rd day post-PDT, whereas volumes increased 6 times in controls. PDT with intravenously (i.v.) administered liposomal (3.2 mg(.)kg(-1)) TPP mostly disintegrated tumours to zero volumes. Melanoma remissions were accompanied by tumour surface necroses and were documented by the appearance of nonturnourous cells with nonpycnotic nuclei. Spatial arrangement of capillaries in remissing tumour was the same as in healthy surrounding tissue. Lower TPP doses (1, 0.3 and 0. 1 mg.kg(-1)) were more or equally efficient than hydrophilic TPPS4 (3.2 mg(.)kg(-1), i.e., sulfonated TPP), i.v. administered also in liposomes. Liposomal TPPS4 only delayed the onset of subsequent tumour growth. Commercial Photosan 3 disintegrated tumours only in doses of approx. 7.5 mg(.)kg(-1); in lower doses it was less efficient than TPPS4. The second PDT cycle (3.2 mg(.)kg(-1) TPP or 7.5 mg(.)kg(-1) Photosan 3), performed in a few unsuccessfully cured mice, predominantly led again to tumour remissions. Since the measured TPP and TPPS4 content in melanomas was similar, these results demonstrate the advantage of PDT with a hydrophobic photosensitizer such as TPP. Photophysical properties of TPP and TPPS4 are equal, but TPP has probably more favorable intracellular distribution, as documented by our studies, which leads to more efficient PDT. Consequently, liposomal TPP is suggested as a potentially suitable efficient preparation for PDT. (C) 2002 Wiley-Liss, Inc.