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Tumor-Specific ONOO– Nanogenerator for Improved Drug Delivery and Enhanced Chemotherapy of Tumor
ACS Nano ( IF 15.8 ) Pub Date : 2021-07-18 , DOI: 10.1021/acsnano.1c01312
Ying Chen 1 , Zi-Hao Li 1 , Pei Pan 1 , Run-Yao Zeng 1 , Xian-Zheng Zhang 1
ACS Nano ( IF 15.8 ) Pub Date : 2021-07-18 , DOI: 10.1021/acsnano.1c01312
Ying Chen 1 , Zi-Hao Li 1 , Pei Pan 1 , Run-Yao Zeng 1 , Xian-Zheng Zhang 1
Affiliation
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Multiple biological barriers in solid tumors severely restrict the penetration of nanomedicines, which is a main cause for therapeutic failure in traditional tumor treatment. Here, a tumor-specific nanogenerator of peroxynitrite (ONOO–), prepared by loading cisplatin and sodium nitroprusside into poly(d,l-lactide-co-glycolide) polymersomes, was designed to improve drug delivery and enhance tumor chemotherapy. After a cascade of nicotinamide adenine dinucleotide phosphate oxidases catalysis and glutathione reduction, the nanogenerator, namely, PMCS, could selectively induce the generation of ONOO– in tumor. The generated ONOO– could not only strengthen vascular permeability significantly but also improve the accumulation and penetration of PMCS in tumor by activating matrix metalloproteinases-mediated degradation of extracellular matrix. Along with endocytosis, PMCS released cisplatin to induce tumor cell apoptosis. Moreover, free cisplatin liberated from dead cells infected neighboring tumor cells quickly via ONOO–-mediated up-regulated copper transporter 1, further amplifying chemotherapeutic efficacy. This study advances ONOO– as a potent modality to address the main issues of therapeutic delivery, including but not limited to chemotherapy.
中文翻译：
肿瘤特异性 ONOO——用于改善药物输送和增强肿瘤化疗的纳米发电机
实体瘤中的多重生物屏障严重限制了纳米药物的渗透，这是传统肿瘤治疗失败的主要原因。在这里，通过将顺铂和硝普钠加载到聚（d，l-丙交酯-共-乙交酯）聚合物囊泡中制备的过氧亚硝酸盐（ONOO - ）肿瘤特异性纳米发生器旨在改善药物递送并增强肿瘤化学疗法。经过烟酰胺腺嘌呤二核苷酸磷酸氧化酶催化和谷胱甘肽还原的级联反应，纳米发电机，即 PMCS，可以选择性地诱导肿瘤中 ONOO-的产生。生成的ONOO——不仅可以显着增强血管通透性，还可以通过激活基质金属蛋白酶介导的细胞外基质降解来改善 PMCS 在肿瘤中的积累和渗透。随着内吞作用，PMCS 释放顺铂以诱导肿瘤细胞凋亡。此外，从死细胞中释放的游离顺铂通过ONOO -介导的上调铜转运蛋白 1 迅速感染邻近的肿瘤细胞，进一步增强了化疗效果。这项研究推进了 ONOO——作为一种有效的方式来解决治疗交付的主要问题，包括但不限于化疗。
更新日期：2021-07-27
中文翻译：
肿瘤特异性 ONOO——用于改善药物输送和增强肿瘤化疗的纳米发电机
实体瘤中的多重生物屏障严重限制了纳米药物的渗透，这是传统肿瘤治疗失败的主要原因。在这里，通过将顺铂和硝普钠加载到聚（d，l-丙交酯-共-乙交酯）聚合物囊泡中制备的过氧亚硝酸盐（ONOO - ）肿瘤特异性纳米发生器旨在改善药物递送并增强肿瘤化学疗法。经过烟酰胺腺嘌呤二核苷酸磷酸氧化酶催化和谷胱甘肽还原的级联反应，纳米发电机，即 PMCS，可以选择性地诱导肿瘤中 ONOO-的产生。生成的ONOO——不仅可以显着增强血管通透性，还可以通过激活基质金属蛋白酶介导的细胞外基质降解来改善 PMCS 在肿瘤中的积累和渗透。随着内吞作用，PMCS 释放顺铂以诱导肿瘤细胞凋亡。此外，从死细胞中释放的游离顺铂通过ONOO -介导的上调铜转运蛋白 1 迅速感染邻近的肿瘤细胞，进一步增强了化疗效果。这项研究推进了 ONOO——作为一种有效的方式来解决治疗交付的主要问题，包括但不限于化疗。
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