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Thiol-Responsive Polypeptide Sulfur Dioxide Prodrug Nanoparticles for Effective Tumor Inhibition
Biomacromolecules ( IF 5.5 ) Pub Date : 2023-08-23 , DOI: 10.1021/acs.biomac.3c00767 Yu Zhang 1 , Xinming Liu 1 , Pan He 2 , Bingtong Tang 2 , Chunsheng Xiao 1 , Xuesi Chen 1
Biomacromolecules ( IF 5.5 ) Pub Date : 2023-08-23 , DOI: 10.1021/acs.biomac.3c00767 Yu Zhang 1 , Xinming Liu 1 , Pan He 2 , Bingtong Tang 2 , Chunsheng Xiao 1 , Xuesi Chen 1
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Sulfur dioxide (SO2) based gas therapy has emerged as a novel anticancer therapeutic strategy because of its high therapeutic efficacy and biosafety. To precisely adjust the SO2 content and control gas release, herein, a thiol-responsive polypeptide SO2 prodrug mPEG-block-poly(2-amino-6-(2,4-dinitrophenylsulfonamido)hexanoic acid) (PEG-b-PLys-DNs) was designed and facilely synthesized by polymerization of a novel N-carboxyanhydride SO2-NCA. The anticancer potential of the self-assembled nanoparticles (SO2-NPs) was investigated in detail. First, PEG-b-PLys-DNs were synthesized by ring-opening polymerization of SO2-NCA, which self-assembled into NPs sized 88.4 nm in aqueous. Subsequently, SO2-NPs were endocytosed into 4T1 cells and quickly released SO2 under a high concentration of glutathione in tumor cells. This process depleted cellular glutathione, generated reactive oxygen species, and dramatically increased oxidative stress, which led to cancer cell apoptosis. Finally, the in vivo anticancer efficacy of SO2-NPs was verified in 4T1-tumor-bearing mice. Our results indicated that this novel SO2 polymeric prodrug has great potential in eradicating tumors.
中文翻译：
硫醇响应性多肽二氧化硫前药纳米颗粒可有效抑制肿瘤
基于二氧化硫（SO 2）的气体疗法因其高治疗效果和生物安全性而成为一种新型的抗癌治疗策略。为了精确调节SO 2含量并控制气体释放，本文提出了硫醇响应性多肽SO 2前药mPEG- block-聚(2-氨基-6-(2,4-二硝基苯基磺酰胺基)己酸)(PEG- b -PLys ) -DNs)是通过新型N-羧酸酐SO 2 -NCA的聚合而设计并轻松合成的。详细研究了自组装纳米粒子（SO 2 -NPs）的抗癌潜力。首先，通过SO 2 -NCA的开环聚合合成了PEG- b -PLys-DNs ，其在水溶液中自组装成尺寸为88.4 nm的NPs。随后，SO 2 -NPs被内吞到4T1细胞中，并在肿瘤细胞内高浓度谷胱甘肽的作用下快速释放SO 2 。这一过程耗尽细胞谷胱甘肽，产生活性氧，并显着增加氧化应激，从而导致癌细胞凋亡。最后，SO 2 -NPs的体内抗癌功效在4T1荷瘤小鼠中得到验证。我们的结果表明这种新型SO 2聚合物前药在根除肿瘤方面具有巨大潜力。
更新日期：2023-08-23
中文翻译：
硫醇响应性多肽二氧化硫前药纳米颗粒可有效抑制肿瘤
基于二氧化硫（SO 2）的气体疗法因其高治疗效果和生物安全性而成为一种新型的抗癌治疗策略。为了精确调节SO 2含量并控制气体释放，本文提出了硫醇响应性多肽SO 2前药mPEG- block-聚(2-氨基-6-(2,4-二硝基苯基磺酰胺基)己酸)(PEG- b -PLys ) -DNs)是通过新型N-羧酸酐SO 2 -NCA的聚合而设计并轻松合成的。详细研究了自组装纳米粒子（SO 2 -NPs）的抗癌潜力。首先，通过SO 2 -NCA的开环聚合合成了PEG- b -PLys-DNs ，其在水溶液中自组装成尺寸为88.4 nm的NPs。随后，SO 2 -NPs被内吞到4T1细胞中，并在肿瘤细胞内高浓度谷胱甘肽的作用下快速释放SO 2 。这一过程耗尽细胞谷胱甘肽，产生活性氧，并显着增加氧化应激，从而导致癌细胞凋亡。最后，SO 2 -NPs的体内抗癌功效在4T1荷瘤小鼠中得到验证。我们的结果表明这种新型SO 2聚合物前药在根除肿瘤方面具有巨大潜力。
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