Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
J Nanobiotechnology. 2019 Apr 5;17(1):50. doi: 10.1186/s12951-019-0475-1.
Improving the water solubility of hydrophobic photosensitizer and increasing its accumulation in tumor tissue are essential for in vivo photodynamic therapy (PDT). Considering commercialization or clinical application in future, it will be promising to achieve these purposes by developing new agents with simple and non-toxic structure.
We conjugated multiple chlorin e6 (Ce6) molecules to gelatin polymer, synthesizing two types of gelatin-Ce6 conjugates with different amounts of Ce6: gelatin-Ce6-2 and gelatin-Ce6-8. The resulting conjugates remained soluble in aqueous solutions for a longer time than hydrophobic Ce6. The conjugates could generate singlet oxygen and kill tumor cells upon laser irradiation. After intravenous injection into SCC-7 tumor-bearing mice, gelatin-Ce6-2 showed prolonged blood circulation and highly increased accumulation in tumor tissue as observed in real-time imaging in vivo. After laser irradiation, gelatin-Ce6-2 suppressed tumor growth completely and enabled improved PDT compared to free Ce6 and gelatin-Ce6-8.
This work demonstrates that a simple structure based on photosensitizer and gelatin can highly improve water solubility and stability. Superior tumor tissue accumulation and increased therapeutic efficacy of gelatin-Ce6 during in vivo PDT showed its high potential for clinical application.
提高疏水性光敏剂的水溶性并增加其在肿瘤组织中的积累对于体内光动力疗法（PDT）至关重要。考虑到未来的商业化或临床应用，通过开发具有简单、无毒结构的新型制剂来实现这些目标将是有前途的。
我们将多个氯卟啉 e6（Ce6）分子偶联到明胶聚合物上，合成了两种具有不同 Ce6 含量的明胶-Ce6 缀合物：明胶-Ce6-2 和明胶-Ce6-8。所得缀合物在水溶液中的溶解度比疏水性 Ce6 更长。这些缀合物在激光照射下可以产生单线态氧并杀死肿瘤细胞。静脉注射到 SCC-7 荷瘤小鼠后，明胶-Ce6-2 在体内实时成像中显示出更长的血液循环时间和高度增加的肿瘤组织积累。激光照射后，明胶-Ce6-2 完全抑制了肿瘤生长，并与游离 Ce6 和明胶-Ce6-8 相比提高了 PDT 的疗效。
这项工作表明，基于光敏剂和明胶的简单结构可以极大地提高水溶性和稳定性。在体内 PDT 过程中，明胶-Ce6 在肿瘤组织中的高蓄积和治疗效果的提高表明其具有很高的临床应用潜力。
