Further improvements in Photodynamic therapy (PDT) necessitate that the dye targets more selectively tumour tissues or neovascularization than healthy cells. Different enzymes such as matrix metalloproteinases (MMPs) are overexpressed in tumour areas. Among these MMPs, gelatinases (MMP-2 and MMP-9) and its activator MMP-14 are known to play a key role in tumour angiogenesis and the growth of many cancers such as glioblastoma multiforme (GBM), an aggressive malignant tumour of the brain. These last years, the concept of photodynamic molecular beacons (PMB) became interesting for controlling the photosensitizer’s ability to generate singlet oxygen (¹O₂) close to target biomolecules as MMPs. We report herein novel PMBs triggered by MMP-2 and/or MMP-9 and/or MMP-14, comprising a photosensitizer and a singlet oxygen quencher linked by MMP cleavable peptide linker (H-GRIGFLRTAKGG-OH). First of all, we focused on the synthesis and the photophysical study of different derivatives photosensitizer-peptide. This preliminary work concluded on an influence of the nature and the distance from the peptide, but not of the position of the photosensitizer in these derivatives on the proteolytic enzymatic action. The nature of the quencher used (a blackberry quencher (BBQ-650) or a black hole quencher (BHQ3)) does not influence the enzymatic action. We also studied the influence of an additional PEG spacer. Finally, the synthesis, the singlet oxygen quenching efficiency and the enzymatic activation of these new MMP- cleavable-PMBs were compared.

光动力疗法（PDT）的进一步改进要求该染料比健康细胞更有选择性地靶向肿瘤组织或新血管形成。不同的酶（例如基质金属蛋白酶（MMP））在肿瘤区域中过表达。在这些MMP中，已知明胶酶（MMP-2和MMP-9）及其激活剂MMP-14在肿瘤血管生成和许多癌症的生长中起着关键作用，例如多形性胶质母细胞瘤（GBM），一种侵袭性恶性肿瘤。脑。最近几年，光动力分子信标（PMB）的概念对于控制光敏剂产生单线态氧（¹ O ₂）作为MMP接近目标生物分子。我们在此报告了由MMP-2和/或MMP-9和/或MMP-14触发的新型PMB，包括光敏剂和由MMP可裂解肽接头（H-GRIGFLRTAKGG-OH）连接的单线态氧猝灭剂。首先，我们专注于不同衍生物光敏剂-肽的合成和光物理研究。这项初步工作的结论是对肽的性质和与肽的距离的影响，而不是对这些衍生物中光敏剂的位置对蛋白水解酶作用的影响。使用的淬灭剂（黑莓淬灭剂（BBQ-650）或黑洞淬灭剂（BHQ3））的性质不影响酶促作用。我们还研究了其他PEG间隔基的影响。最后，综合