Porphyrin Dimers for Photodynamic Therapy

光动力疗法(PDT)是一种治疗各种癌症(特别是肺癌、头颈部和非黑色素瘤皮肤癌)和治疗一种被称为急性黄斑变性(AMD)的疾病的成熟方法，AMD是50岁以上人群失明的主要原因。光动力疗法是通过向患者体内注射一种染料，然后用红光照射身体的患病区域来进行的。光能被染料吸收并转移到分子氧中，产生激发的单线态氧，从而杀死周围的细胞。光由称为光子的粒子组成。通常情况下，染料一次只能吸收一个光子，但在高光强下，一些分子能够同时吸收两个光子，这一过程被称为“双光子吸收”(TPA)。通过TPA进行PDT的可能性应该会使这种类型的治疗更适用于更深层次的肿瘤，以及空间选择性至关重要的病例，如脑瘤和眼内异常血管(AMD)。最近，我们发现一类被称为“共轭卟啉低聚物”的染料在近红外波段对双光子光动力学和单光子光动力学具有独特的优势。这个后续项目的主要目标是了解这些药物的疗效，特别是治疗肿瘤的效果。我们还将证明，这些化合物可以在合适的规模上合成，用于未来的临床前和临床试验。这些进展对于通过许可协议使该技术具有商业化吸引力至关重要。

Photodynamic therapy (PDT) is an established method for treating a variety of cancers (particularly lung, head, neck and non-melanoma skin cancer) and for treating a disease known as acute macular degeneration (AMD), which is the main cause of blindness in people over 50. PDT is carried out by injecting a dye into the patient, then irradiating the sick region of the body with red light. The light energy is absorbed by the dye and transferred to molecular oxygen generating excited singlet oxygen, which kills the surrounding cells. Light consists of particles called photons. Normally dyes absorb just one photon at a time, but at high light intensities, some molecules are able to absorb two photons simultaneously in a process known as 'two-photon absorption' (TPA). The possibility of carrying out PDT by TPA should make this type of therapy more applicable to deeper tumours, and to cases where spatial selectivity is critical, such as brain tumours and abnormal blood vessels in the eye (AMD). Recently we have shown that a class of dyes known as 'conjugated porphyrin oligomers' have unique advantages for two-photon PDT, and for one-photon PDT at near-IR wavelengths. The primary objective of this follow-on project is to gain understanding of the efficacy of these drugs, particularly for the treatment of tumours. We will also demonstrate that these compounds can be synthesised on a suitable scale for future pre-clinical and clinical trials. These advances are critical for making the technology attractive for commercialisation through licensing agreements.