Antiangiogenic photodynamic therapy (PDT) by using long-circulating liposomes modified with peptide specific to angiogenic vessels
Antiangiogenic photodynamic therapy (PDT) by using long-circulating liposomes modified with peptide specific to angiogenic vessels
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DOI：
10.1016/j.bbamem.2005.02.003
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发表时间：
2005-05-15
影响因子：
3.4
通讯作者：
Oku, N
中科院分区：
文献类型：
--
作者：
Ichikawa, K;Hikita, T;Oku, N
为了利用光敏剂苯并卟啉衍生物单酸环A(BPD-MA)提高光动力疗法(PDT)的疗效，我们预先制备了聚乙二醇化修饰的BPD-MA脂质体(PEG-Lip BPD-MA)。脂质体的聚乙二醇化促进了BPD-MA注射后3h在荷瘤小鼠体内的蓄积，但在注射脂质体光敏剂后3h进行激光照射时，却意外地降低了该药物对PDT的适合性。为了提高PEG-Lip BPD-MA的生物利用度，我们用丙氨酸-Pro-精氨酸-Pro-甘氨酸(Ala-Pro-Arg-Pro-Gly，APRPG)五肽(APRPG)赋予脂质体活性靶向性，这是一种早期分离的血管生成细胞特异性多肽。APRPG-PEG修饰的脂质体BPD-MA(APRPG-PEG-Lip BPD-MA)在肿瘤组织中的蓄积类似于PEG-Lip BPD-MA。在荷瘤小鼠体内注射药物后3h，BPD-MA的给药程度是未修饰脂质体的4倍。反之，APRPG-PEG-Lip BPD-MA在激光照射后3h即可明显抑制肿瘤生长，而不同于注射后3h的治疗。最后，我们观察了APRPG-PEG-Lip bpd-MA介导的PDT对后气囊血管生成模型血管的损伤。这些结果表明，抗血管生成PDT是一种有效的肿瘤治疗手段，肿瘤新生血管靶向长循环脂质体是将光敏剂输送到血管新生血管内皮细胞的有效载体。(C)2005 Elsevier B.V.保留所有权利。
For the improvement of therapeutic efficacy in photodynamic therapy (PDT) by using a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), we previously prepared polyethylene glycol (PEG)-modified liposomes encapsulating BPD-MA (PEG-Lip BPD-MA). PEGylation of liposomes enhanced the accumulation of BPD-MA in tumor tissue at 3 h after injection of it into Meth-A-sarcoma-bearing mice, but, unexpectedly, decreased the suitability of the drug for PDT when laser irradiation was performed at 3 h after the injection of the liposomal photosensitizer. To improve the bioavailability of PEG-Lip BPD-MA, we endowed the liposomes with active-targeting characteristics by using Ala-Pro-Arg-Pro-Gly (APRPG) pentapeptide, which had earlier been isolated as a peptide specific to angiogenic endothelial cells. APRPG-PEG-modified liposomal BPD-MA (APRPG-PEG-Lip BPD-MA) accumulated in tumor tissue similarly as PEG-Lip BPD-MA and to an approx. 4-fold higher degree than BPD-MA delivered with non-modified liposomes at 3 h after the injection of the drugs into tumor-bearing mice. On the contrary, unlike the treatment with PEG-Lip BPD-MA, APRPG-PEG-Lip BPD-MA treatment strongly suppressed tumor growth after laser irradiation at 3 h after injection. Finally, we observed vasculature damage in the dorsal air sac angiogenesis model by APRPG-PEG-Lip BPD-MA-mediated PDT. The present results suggest that antiangiogenic PDT is an efficient modality for tumor treatment and that tumor neovessel-targeted, long-circulating liposomes are a useful carrier for delivering photosensitizer to angiogenic endothelial cells. (C) 2005 Elsevier B.V. All rights reserved.