Dhaini Batoul, Daouk Joël, Schohn Hervé, Arnoux Philippe, Jouan-Hureaux Valérie, Moussaron Albert, Hagege Agnès, Achard Mathilde, Acherar Samir, Hamieh Tayssir, Frochot Céline
Université de Lorraine, CNRS, LRGP, F-54000 Nancy, France.
Laboratory of Materials, Catalysis, Environment and Analytical Methods (MCEMA), Faculty of Sciences I, Lebanese University, Beirut P.O. Box 6573/1, Lebanon.
Pharmaceuticals (Basel). 2025 May 1;18(5):672. doi: 10.3390/ph18050672.
In order to find a good candidate for Förster Resonance Energy Transfer (FRET)-mediated X-ray-induced photodynamic therapy (X-PDT) for the treatment of cancer, lanthanide (Ln)-based AGuIX nanoparticles (NPs) conjugated with Rose Bengal (RB) as a photosensitizer (PS) were synthesized. X-PDT overcomes the problem of the poor penetration of visible light into tissues, which limits the efficacy of PDT in the treatment of deep-seated tumors. It is essential to optimize FRET efficiency by maximizing the overlap integral between donor emission and acceptor absorption and lengthening the duration of the donor emission. In this study, we optimized energy transfer between a scintillator (Sc) as a donor and a PS as an acceptor. Terbium (Tb) and Gadolinium (Gd) as Scs and Rose RB as a PS were chosen. The study of energy transfer between Tb, Gd and RB in solution and chelated on AGuIX NPs proved to be FRET-like. RB was conjugated directly onto AGuIX NPs (i.e., AGuIX Ln@RB), and the use of a spacer arm (i.e., AGuIX Ln@spacer arm-RB) increased FRET efficiency. Singlet oxygen production by these NPs was observed under UV-visible illumination and X-ray irradiation. The in vitro bioassay demonstrated 52% cell death of U-251MG derived from human malignant glioblastoma multiforme at a concentration of 1 μM RB after illumination and irradiation (2 Gy, 320 kV, 10 mA, 3 Gy/min at 47 cm). In addition, the RB-coupled NRP-1-targeting peptide (i.e., K(RB)DKPPR) was conjugated onto AGuIX NPs by a thiol-maleimide click chemistry reaction, and an affinity in the nM range was observed.
为了找到一种用于癌症治疗的基于荧光共振能量转移（FRET）介导的X射线诱导光动力疗法（X-PDT）的优良候选物，合成了与作为光敏剂（PS）的孟加拉玫瑰红（RB）共轭的镧系（Ln）基AGuIX纳米颗粒（NPs）。X-PDT克服了可见光对组织穿透性差的问题，而这一问题限制了PDT在深部肿瘤治疗中的疗效。通过最大化供体发射与受体吸收之间的重叠积分并延长供体发射持续时间来优化FRET效率至关重要。在本研究中，我们优化了作为供体的闪烁体（Sc）与作为受体的PS之间的能量转移。选择了铽（Tb）和钆（Gd）作为Sc，玫瑰红RB作为PS。对溶液中以及螯合在AGuIX NPs上的Tb、Gd和RB之间的能量转移研究证明具有类FRET性质。RB直接共轭到AGuIX NPs上（即AGuIX Ln@RB），使用间隔臂（即AGuIX Ln@间隔臂-RB）提高了FRET效率。在紫外-可见光照射和X射线照射下观察到这些NPs产生单线态氧。体外生物测定表明，在光照和照射（2 Gy，320 kV，10 mA，47 cm处3 Gy/min）后，浓度为1 μM RB时，源自人多形性恶性胶质母细胞瘤的U-251MG细胞有52%死亡。此外，通过硫醇-马来酰亚胺点击化学反应将RB偶联的NRP-1靶向肽（即K(RB)DKPPR）共轭到AGuIX NPs上，并观察到其在纳摩尔范围内的亲和力。
