癌细胞选择性杀伤聚合物/铜组合
Cancer cell-selective killing polymer/copper combination.
作者信息
He Huacheng, Altomare Diego, Ozer Ufuk, Xu Hanwen, Creek Kim, Chen Hexin, Xu Peisheng
机构信息
Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA.
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
出版信息
Biomater Sci. 2016 Jan;4(1):115-20. doi: 10.1039/c5bm00325c.
Abstract
Chemotherapy has been adopted for cancer treatment for decades. However, its efficacy and safety are frequently compromised by the multidrug-resistance of cancer cells and the poor cancer cell selectivity of anticancer drugs. Hereby, we report a combination of a pyridine-2-thiol containing polymer and copper which can effectively kill a wide spectrum of cancer cells, including drug resistant cancer cells, while sparing normal cells. The polymer nanoparticle enters cells via an exofacial thiol facilitated route, and releases active pyridine-2-thiol with the help of intracellularly elevated glutathione (GSH). Due to their high GSH level, cancer cells are more vulnerable to the polymer/copper combination. In addition, RNA microarray analysis revealed that the treatment can reverse cancer cells' upregulated oncogenes (CIRBP and STMN1) and downregulated tumor suppressor genes (CDKN1C and GADD45B) to further enhance the selectivity for cancer cells.
摘要
几十年来，化疗一直被用于癌症治疗。然而，其疗效和安全性常常受到癌细胞多药耐药性以及抗癌药物对癌细胞选择性差的影响。在此，我们报告了一种含吡啶 - 2 - 硫醇的聚合物与铜的组合，它能有效杀死包括耐药癌细胞在内的多种癌细胞，同时对正常细胞无害。聚合物纳米颗粒通过外表面硫醇促进的途径进入细胞，并在细胞内升高的谷胱甘肽（GSH）的帮助下释放活性吡啶 - 2 - 硫醇。由于癌细胞的谷胱甘肽水平较高，它们更容易受到聚合物/铜组合的影响。此外，RNA微阵列分析表明，该治疗可逆转癌细胞中上调的癌基因（CIRBP和STMN1）和下调的肿瘤抑制基因（CDKN1C和GADD45B），从而进一步增强对癌细胞的选择性。
相似文献
1
Cancer cell-selective killing polymer/copper combination.癌细胞选择性杀伤聚合物/铜组合
Biomater Sci. 2016 Jan;4(1):115-20. doi: 10.1039/c5bm00325c.
2
Lenvatinib-zinc phthalocyanine conjugates as potential agents for enhancing synergistic therapy of multidrug-resistant cancer by glutathione depletion.镧系元素酞菁锌配合物作为通过谷胱甘肽耗竭增强多药耐药性癌症协同治疗的潜在药物。
Eur J Med Chem. 2019 May 1;169:53-64. doi: 10.1016/j.ejmech.2019.02.065. Epub 2019 Mar 4.
3
Maleimide-functionalised organoruthenium anticancer agents and their binding to thiol-containing biomolecules.马来酰亚胺功能化的有机钌抗肿瘤试剂及其与含巯基生物分子的结合。
Chem Commun (Camb). 2012 Feb 1;48(10):1475-7. doi: 10.1039/c1cc14713g. Epub 2011 Oct 14.
4
Redox active copper chelate overcomes multidrug resistance in T-lymphoblastic leukemia cell by triggering apoptosis.氧化还原活性铜螯合物通过引发细胞凋亡克服T淋巴细胞白血病细胞中的多药耐药性。
Mol Biosyst. 2011 May;7(5):1701-12. doi: 10.1039/c0mb00306a. Epub 2011 Mar 15.
5
An organoruthenium complex overcomes ABCG2-mediated multidrug resistance via multiple mechanisms.一种有机钌配合物通过多种机制克服 ABCG2 介导的多药耐药性。
Chem Commun (Camb). 2019 Mar 26;55(26):3833-3836. doi: 10.1039/c9cc00882a.
6
A glutathione-responsive sulfur dioxide polymer prodrug as a nanocarrier for combating drug-resistance in cancer chemotherapy.一种响应谷胱甘肽的二氧化硫聚合物前药作为纳米载体用于克服癌症化疗中的耐药性。
Biomaterials. 2018 Sep;178:706-719. doi: 10.1016/j.biomaterials.2018.02.011. Epub 2018 Feb 3.
7
Elevated glutathione levels confer cellular sensitization to cisplatin toxicity by up-regulation of copper transporter hCtr1.谷胱甘肽水平升高通过上调铜转运蛋白hCtr1使细胞对顺铂毒性敏感。
Mol Pharmacol. 2008 Sep;74(3):697-704. doi: 10.1124/mol.108.047969. Epub 2008 Jun 3.
8
Synthesis of copper and zinc 2-(pyridin-2-yl)imidazo[1,2-a]pyridine complexes and their potential anticancer activity.铜和锌的2-(吡啶-2-基)咪唑并[1,2-a]吡啶配合物的合成及其潜在的抗癌活性。
Eur J Med Chem. 2017 Jan 27;126:353-368. doi: 10.1016/j.ejmech.2016.10.041. Epub 2016 Nov 11.
9
Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH efflux.耐药 MRP1 过度表达细胞通过 GSH 外排对黄酮类化合物和衍生物的旁敏感作用。
Biochem Pharmacol. 2014 Aug 1;90(3):235-45. doi: 10.1016/j.bcp.2014.05.017. Epub 2014 May 27.
10
Biofunctionalized polymer-lipid supported mesoporous silica nanoparticles for release of chemotherapeutics in multidrug resistant cancer cells.用于在多药耐药癌细胞中释放化疗药物的生物功能化聚合物-脂质支撑的介孔硅纳米粒子。
Biomaterials. 2014 Apr;35(11):3650-65. doi: 10.1016/j.biomaterials.2014.01.013. Epub 2014 Jan 24.
引用本文的文献
1
Polymer/copper nanocomplex-induced lysosomal cell death promotes tumor lymphocyte infiltration and synergizes anti-PD-L1 immunotherapy for triple-negative breast cancer.聚合物/铜纳米复合物诱导的溶酶体细胞死亡促进肿瘤淋巴细胞浸润，并与抗 PD-L1 免疫疗法协同作用治疗三阴性乳腺癌。
Biomater Sci. 2023 Aug 8;11(16):5641-5652. doi: 10.1039/d3bm00627a.
2
Enhanced drug delivery to cancer cells through a pH-sensitive polycarbonate platform.通过 pH 敏感型聚碳酸酯平台增强向癌细胞的药物传递。
Biomater Sci. 2023 Jan 31;11(3):908-915. doi: 10.1039/d2bm01626e.
3
Peptide-Based Bioconjugates and Therapeutics for Targeted Anticancer Therapy.用于靶向抗癌治疗的基于肽的生物共轭物和疗法。
Pharmaceutics. 2022 Jun 29;14(7):1378. doi: 10.3390/pharmaceutics14071378.
4
Activated Bone Marrow-Derived Macrophages Eradicate Alzheimer's-Related Aβ Oligomers and Protect Synapses.激活的骨髓衍生巨噬细胞可消除阿尔茨海默病相关的 Aβ 寡聚物并保护突触。
Front Immunol. 2020 Jan 31;11:49. doi: 10.3389/fimmu.2020.00049. eCollection 2020.
5
A bioactivatable self-quenched nanogel for targeted photodynamic therapy.一种可激活自猝灭的纳米凝胶用于靶向光动力疗法。
Biomater Sci. 2019 Dec 1;7(12):5143-5149. doi: 10.1039/c9bm01237k. Epub 2019 Oct 2.
6
Repurposing disulfiram for cancer therapy via targeted nanotechnology through enhanced tumor mass penetration and disassembly.通过增强肿瘤质量渗透和分解，通过靶向纳米技术将双硫仑重新用于癌症治疗。
Acta Biomater. 2018 Mar 1;68:113-124. doi: 10.1016/j.actbio.2017.12.023. Epub 2017 Dec 30.
7
Recent progress in the research of cold-inducible RNA-binding protein.冷诱导RNA结合蛋白的研究进展
Future Sci OA. 2017 Oct 4;3(4):FSO246. doi: 10.4155/fsoa-2017-0077. eCollection 2017 Nov.
8
Redox Potential-Sensitive N-Acetyl Cysteine-Prodrug Nanoparticles Inhibit the Activation of Microglia and Improve Neuronal Survival.氧化还原电位敏感的N-乙酰半胱氨酸前药纳米颗粒抑制小胶质细胞的激活并改善神经元存活。
Mol Pharm. 2017 May 1;14(5):1591-1600. doi: 10.1021/acs.molpharmaceut.6b01028. Epub 2017 Apr 4.
9
Cold-inducible proteins CIRP and RBM3, a unique couple with activities far beyond the cold.冷诱导蛋白CIRP和RBM3，一对具有远超寒冷相关活性的独特组合。
Cell Mol Life Sci. 2016 Oct;73(20):3839-59. doi: 10.1007/s00018-016-2253-7. Epub 2016 May 4.
本文引用的文献
1
Cold-inducible RNA-binding protein promotes the development of liver cancer.冷诱导RNA结合蛋白促进肝癌发展。
Cancer Sci. 2015 Apr;106(4):352-8. doi: 10.1111/cas.12611. Epub 2015 Mar 3.
2
On the interaction of copper(II) with disulfiram.关于铜（II）与双硫仑的相互作用。
Chem Commun (Camb). 2014 Nov 11;50(87):13334-7. doi: 10.1039/c4cc04767b. Epub 2014 Sep 18.
3
Stress response protein cirp links inflammation and tumorigenesis in colitis-associated cancer.应激反应蛋白 cirp 在结肠炎相关癌症中的炎症和肿瘤发生中起作用。
Cancer Res. 2014 Nov 1;74(21):6119-28. doi: 10.1158/0008-5472.CAN-14-0471. Epub 2014 Sep 3.
4
Triple-responsive expansile nanogel for tumor and mitochondria targeted photosensitizer delivery.用于肿瘤和线粒体靶向光敏剂递送的三响应性可膨胀纳米凝胶
Biomaterials. 2014 Nov;35(35):9546-53. doi: 10.1016/j.biomaterials.2014.08.004. Epub 2014 Aug 22.
5
Expression of Stathmin1 in gastric adenocarcinoma.Stathmin1 在胃腺癌中的表达。
Anticancer Res. 2014 Aug;34(8):4217-21.
6
GADD45 proteins: roles in cellular senescence and tumor development.生长停滞和DNA损伤诱导蛋白45（GADD45）家族蛋白：在细胞衰老和肿瘤发生中的作用
Exp Biol Med (Maywood). 2014 Jul;239(7):773-778. doi: 10.1177/1535370214531879. Epub 2014 May 28.
7
Redox potential ultrasensitive nanoparticle for the targeted delivery of camptothecin to HER2-positive cancer cells.用于将喜树碱靶向递送至HER2阳性癌细胞的氧化还原电位超灵敏纳米颗粒。
Mol Pharm. 2014 Jun 2;11(6):1897-905. doi: 10.1021/mp5000482. Epub 2014 May 9.
8
Multifunctional tumor pH-sensitive self-assembled nanoparticles for bimodal imaging and treatment of resistant heterogeneous tumors.多功能肿瘤 pH 敏感自组装纳米粒子用于耐药异质肿瘤的双模式成像和治疗。
J Am Chem Soc. 2014 Apr 16;136(15):5647-55. doi: 10.1021/ja4108287. Epub 2014 Apr 1.
9
STMN-1 is a potential marker of lymph node metastasis in distal esophageal adenocarcinomas and silencing its expression can reverse malignant phenotype of tumor cells.STMN-1是远端食管腺癌淋巴结转移的潜在标志物，沉默其表达可逆转肿瘤细胞的恶性表型。
BMC Cancer. 2014 Jan 16;14:28. doi: 10.1186/1471-2407-14-28.
10
Cancer statistics, 2014.癌症统计数据，2014 年。
CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29. doi: 10.3322/caac.21208. Epub 2014 Jan 7.
Zotero 插件