Musib Dulal, Upadhyay Aarti, Pal Maynak, Raza Md Kausar, Saha Indranil, Kunwar Amit, Roy Mithun
Department of Chemistry, National Institute of Technology Manipur, Langol, Imphal West, 795004, India.
Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore, CV Raman Avenue, Bangalore 560012, India.
J Inorg Biochem. 2023 Jun;243:112183. doi: 10.1016/j.jinorgbio.2023.112183. Epub 2023 Mar 11.
We report the synthesis and characterization of red-light activable gold nanoparticle functionalized with biotinylated copper(II) complex of general molecular formula, [Cu(L)(L)]-AuNPs (Biotin-Cu@AuNP), where L = N-(3-((E)-3,5-di-tert-butyl-2-hydroxybenzylideneamino)-4-hydroxyphenyl)-5-((3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide, L = 5-(1,2-dithiolan-3-yl)-N-(1,10-phenanthrolin-5-yl)pentanamide, which was explored for their photophysical, theoretical and photo-cytotoxic potentials. The nanoconjugate exhibits differential uptake in biotin positive and biotin negative cancer cells as well as normal cells. The nanoconjugate also shows remarkable photodynamic activity against biotin positive A549 (IC: 13 μg/mL in red light; >150 μg/mL in dark) and HaCaT (IC: 23 μg/mL in red light; >150 μg/mL in dark) cells under red light (600-720 nm, 30 Jcm) irradiation, with significantly high photo-indices (PI>15). The nanoconjugate is less toxic to HEK293T (biotin negative) and HPL1D (normal) cells. Confocal microscopy confirms preferential mitochondrial and partly cytoplasmic localization of Biotin-Cu@AuNP in A549 cells. Several photo-physical and theoretical studies reveal the red light-assisted generation of singlet oxygen (O) (Ф (O) =0.68) as a reactive oxygen species (ROS) which results in remarkable oxidative stress and mitochondrial membrane damage, leading to caspase 3/7-dependent apoptosis of A549 cells. Overall, the nanocomposite (Biotin-Cu@AuNP) exhibiting red light-assisted targeted photodynamic activity has emerged as the ideal next generation PDT agents.
我们报道了通式为[Cu(L)(L)]-AuNPs（生物素-Cu@AuNP）的生物素化铜（II）配合物功能化的红光可激活金纳米颗粒的合成与表征，其中L = N-(3-((E)-3,5-二叔丁基-2-羟基苄叉氨基)-4-羟基苯基)-5-((3aS,4S,6aR)-2-氧代-六氢-1H-噻吩并[3,4-d]咪唑-4-基)戊酰胺，L = 5-(1,2-二硫杂环戊烷-3-基)-N-(1,10-菲啰啉-5-基)戊酰胺，并对其光物理、理论和光细胞毒性潜力进行了探索。该纳米共轭物在生物素阳性和生物素阴性癌细胞以及正常细胞中表现出不同的摄取情况。该纳米共轭物在红光（600 - 720 nm，30 J/cm²）照射下，对生物素阳性的A549细胞（红光下IC₅₀：13 μg/mL；黑暗中>150 μg/mL）和HaCaT细胞（红光下IC₅₀：23 μg/mL；黑暗中>150 μg/mL）也显示出显著的光动力活性，光指数显著较高（PI>15）。该纳米共轭物对HEK293T（生物素阴性）和HPL1D（正常）细胞的毒性较小。共聚焦显微镜证实生物素-Cu@AuNP在A549细胞中优先定位于线粒体和部分细胞质。多项光物理和理论研究表明，红光辅助产生单线态氧（¹O₂）（Ф(¹O₂)=0.68）作为活性氧（ROS），导致显著的氧化应激和线粒体膜损伤，从而导致A549细胞依赖半胱天冬酶3/7的凋亡。总体而言，表现出红光辅助靶向光动力活性的纳米复合材料（生物素-Cu@AuNP）已成为理想的下一代光动力治疗剂。
