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Hypoxia/pH dual-responsive nitroimidazole-modified chitosan/rose bengal derivative nanoparticles for enhanced photodynamic anticancer therapy
Dyes and Pigments ( IF 4.1 ) Pub Date : 2020-03-29 , DOI: 10.1016/j.dyepig.2020.108395
Xudong Li , Jun Wang , Ranran Cui , Dekang Xu , Lisheng Zhu , Ziying Li , Haijun Chen , Yu Gao , Lee Jia

Most of the traditional photosensitizers (PSs) used in photodynamic therapy (PDT) have poor tumor targeting and phototoxic side effects. Drug delivery systems can be designed to be triggered to release payload PSs in response to intracellular hypoxia and acidic environment of tumors with controllable photoactivity to achieve enhanced therapeutic effects with minimal side-effects. In this work, we synthesized nitroimidazole-modified chitosan (Cs-NA) and prepared Cs-NA/rose bengal ω-carboxyheptyl ester (a rose bengal derivative, RBD) complex nanoparticles (Cs-NA/RBD) for pH and hypoxia double-responsive RBD delivery. Cs-NA/RBD possessed appropriate particle size of about 86.9 nm and zeta potential of +33.4 mV, showed good stability in cell culture medium, and demonstrated increased accumulative release at acidic and hypoxia condition by about 60% compared to that at neutral pH. The cellular uptake efficiency of Cs-NA/RBD in non-small cell lung cancer PC9 cells increased more than 10 times compared with Cs-NA/RB. The anti-proliferative effects and the generation of reactive oxygen species (ROS) in PC9 cells indicated the notable photodynamic therapeutic effects of Cs-NA/RBD. These results suggested that Cs-NA/RBD could be a promising nanoplatform for enhanced controllable photodynamic anticancer therapy.



中文翻译:

低氧/ pH双响应硝基咪唑修饰的壳聚糖/玫瑰孟加拉衍生物纳米粒子增强光动力抗癌治疗

在光动力疗法(PDT)中使用的大多数传统光敏剂(PSs)具有很差的肿瘤靶向性和光毒副作用。可以设计药物递送系统,以响应具有可控光活性的肿瘤的细胞内缺氧和酸性环境而触发释放有效载荷PS,从而以最小的副作用实现增强的治疗效果。在这项工作中,我们合成了硝基咪唑改性的壳聚糖(Cs-NA),并制备了具有pH和缺氧双重作用的Cs-NA /玫瑰孟加拉ω-羧基庚酯(玫瑰孟加拉衍生物,RBD)复合纳米粒子(Cs-NA / RBD)。响应式RBD交付。Cs-NA / RBD的合适粒径约为86.9 nm,ζ电位为+33.4 mV,在细胞培养基中显示出良好的稳定性,与酸性和低氧条件下的累积释放相比,在中性pH下的累积释放增加了约60%。与Cs-NA / RB相比,非小细胞肺癌PC9细胞中Cs-NA / RBD的细胞吸收效率提高了10倍以上。PC9细胞的抗增殖作用和活性氧(ROS)的产生表明Cs-NA / RBD具有显着的光动力治疗作用。这些结果表明,Cs-NA / RBD可能是一种有前途的纳米平台,可用于增强可控的光动力抗癌治疗。PC9细胞的抗增殖作用和活性氧(ROS)的产生表明Cs-NA / RBD具有显着的光动力治疗作用。这些结果表明,Cs-NA / RBD可能是一种有前途的纳米平台,可用于增强可控的光动力抗癌治疗。PC9细胞的抗增殖作用和活性氧(ROS)的产生表明Cs-NA / RBD具有显着的光动力治疗作用。这些结果表明,Cs-NA / RBD可能是一种有前途的纳米平台,可用于增强可控的光动力抗癌治疗。

更新日期:2020-03-30
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