School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT97BL, UK.
Future Med Chem. 2009 Jul;1(4):667-91. doi: 10.4155/fmc.09.55.
Photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) are techniques that combine the effects of visible light irradiation with subsequent biochemical events that arise from the presence of a photosensitizing drug (possessing no dark toxicity) to cause destruction of selected cells. Despite its still widespread clinical use, Photofrin(®) has several drawbacks that limit its general clinical use. Consequently, there has been extensive research into the design of improved alternative photosensitizers aimed at overcoming these drawbacks. While there are many review articles on the subject of PDT and PACT, these have focused on the photosensitizers that have been used clinically, with little emphasis placed on how the chemical aspects of the molecule can affect their efficacy as PDT agents. Indeed, many of the PDT/PACT agents used clinically may not even be the most appropriate within a given class. As such, this review aims to provide a better understanding of the factors that have been investigated, while aiming at improving the efficacy of a molecule intended to be used as a photosensitizer. Recent publications, spanning the last 5 years, concerning the design, synthesis and clinical usage of photosensitizers for application in PDT and PACT are reviewed, including 5-aminolevulinic acid, porphyrins, chlorins, bacteriochlorins, texaphyrins, phthalocyanines and porphycenes. It has been shown that there are many important considerations when designing a potential PDT/PACT agent, including the influence of added groups on the lipophilicity of the molecule, the positioning and nature of these added groups within the molecule, the presence of a central metal ion and the number of charges that the molecule possesses. The extensive ongoing research within the field has led to the identification of a number of potential lead molecules for application in PDT/PACT. The development of the second-generation photosensitizers, possessing shorter periods of photosensitization, longer activation wavelengths and greater selectivity for diseased tissue provides hope for attaining the ideal photosensitizer that may help PDT and PACT move from laboratory investigation to clinical practice.
光动力疗法（PDT）和光动力抗菌化疗（PACT）是将可见光照射与随后由光敏药物（无暗毒性）存在引起的生化事件相结合的技术，以引起选定细胞的破坏。尽管 Photofrin(®) 在临床上仍广泛使用，但它存在一些缺点，限制了其在临床上的广泛应用。因此，已经进行了广泛的研究，旨在设计改进的替代光敏剂，以克服这些缺点。尽管有许多关于 PDT 和 PACT 的综述文章，但这些文章都集中在临床上使用的光敏剂上，很少强调分子的化学方面如何影响其作为 PDT 剂的疗效。事实上，临床上使用的许多 PDT/PACT 剂甚至可能不是在特定类别中最合适的。因此，本综述旨在更好地理解已研究的因素，同时旨在提高作为光敏剂使用的分子的疗效。回顾了过去 5 年中有关用于 PDT 和 PACT 的光敏剂的设计、合成和临床应用的最新出版物，包括 5-氨基酮戊酸、卟啉、氯卟啉、细菌卟啉、四嗪、酞菁和卟吩。已经表明，在设计潜在的 PDT/PACT 剂时，有许多重要的考虑因素，包括添加基团对分子亲脂性的影响、这些添加基团在分子中的位置和性质、中心金属离子的存在以及分子所具有的电荷数。该领域正在进行的广泛研究导致了一些潜在的用于 PDT/PACT 的先导分子的鉴定。第二代光敏剂的发展，具有较短的光敏化时间、更长的激活波长和对病变组织更高的选择性，为获得理想的光敏剂提供了希望，这可能有助于 PDT 和 PACT 从实验室研究走向临床实践。
