Université de Lorraine, CNRS, LRGP, F-54000 Nancy, France.
Université de Lorraine, CNRS, LCPM, F-54000 Nancy, France.
ACS Appl Bio Mater. 2021 Feb 15;4(2):1330-1339. doi: 10.1021/acsabm.0c01227. Epub 2021 Jan 11.
Photodynamic therapy (PDT) is a promising technique to treat different kinds of disease especially cancer. PDT requires three elements: molecular oxygen, a photoactivatable molecule called the photosensitizer (PS), and appropriate light. Under illumination, the PSs generate, in the presence of oxygen, the formation of reactive oxygen species including singlet oxygen, toxic, which then destroys the surrounding tissues. Even if PDT is used with success to treat actinic keratosis or prostate cancer for example, PDT suffers from two major drawbacks: the lack of selectivity of most of the PSs currently used clinically as well as the need for oxygen to be effective. To remedy the lack of selectivity, targeting the tumor neovessels is a promising approach to destroy the vascularization and cause asphyxia of the tumor. KDKPPR peptide affinity for the neuropilin-1 (NRP-1) receptor overexpressed on endothelial cells has already been proven. To compensate for the lack of oxygen, we focused on photoactivatable alkoxyamines (Alks), molecules capable of generating toxic radicals by light activation. In this article, we describe the synthesis of a multifunctional platform combining three units: a PS for an oxygen-dependent PDT, a peptide to target tumor neovessels, and an Alk for an oxygen-independent activity. The synthesis of the compound was successfully carried out, and the study of its photophysical properties showed that the PS retained its capacity to form singlet oxygen and the affinity tests confirmed the affinity of the compound for NRP-1. Thanks to the electron paramagnetic resonance spectroscopy, a technique of choice for radical investigation, the radicals generated by the illumination of the Alk could be detected. The proof of concept was thus successfully established.
光动力疗法（PDT）是一种有前途的治疗各种疾病的技术，尤其是癌症。PDT 需要三个要素：分子氧、一种称为光敏剂（PS）的光活化分子，以及适当的光。在光照下，PS 在氧气存在下生成活性氧物种，包括单线态氧，有毒的，然后破坏周围组织。即使 PDT 成功用于治疗光化性角化病或前列腺癌等疾病，PDT 也存在两个主要缺点：目前临床使用的大多数 PS 缺乏选择性，以及需要氧气才能有效。为了弥补缺乏选择性，靶向肿瘤新生血管是一种有前途的方法，可以破坏血管化并导致肿瘤窒息。KDKPPR 肽与内皮细胞过度表达的神经纤毛蛋白-1（NRP-1）受体的亲和力已经得到证实。为了弥补氧气的缺乏，我们专注于光活化烷氧基胺（Alks），这些分子能够通过光激活产生有毒自由基。在本文中，我们描述了一种多功能平台的合成，该平台结合了三个单元：一种用于依赖氧的 PDT 的 PS、一种用于靶向肿瘤新生血管的肽和一种用于非依赖氧的活性的 Alk。化合物的合成成功进行，其光物理性质的研究表明 PS 保留了形成单线态氧的能力，亲和性测试证实了该化合物对 NRP-1 的亲和力。得益于电子顺磁共振波谱学，这是一种用于自由基研究的首选技术，可以检测到 Alk 光照产生的自由基。因此，概念验证成功建立。
