Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNA

Abstract Cisplatin (DDP) is a common therapeutic option for non‐small cell lung carcinoma (NSCLC). However, some patients fail to respond to the DDP chemotherapy. Therefore, identifying novel biomarkers to improve the diagnosis and treatment of NSCLC is important. Ubiquitin‐specific protease (USP14)...

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Main Authors: Xinmin Zhao, Xianghua Wu, Huijie Wang, Songtao Lai, Jialei Wang
Format: Article
Language:English
Published: Wiley 2023-04-01
Series:MedComm
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Online Access:https://doi.org/10.1002/mco2.237
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author Xinmin Zhao
Xianghua Wu
Huijie Wang
Songtao Lai
Jialei Wang
author_facet Xinmin Zhao
Xianghua Wu
Huijie Wang
Songtao Lai
Jialei Wang
author_sort Xinmin Zhao
collection DOAJ
description Abstract Cisplatin (DDP) is a common therapeutic option for non‐small cell lung carcinoma (NSCLC). However, some patients fail to respond to the DDP chemotherapy. Therefore, identifying novel biomarkers to improve the diagnosis and treatment of NSCLC is important. Ubiquitin‐specific protease (USP14) is involved in various pathological conditions including cancer; however, the role of USP14 in NSCLC remains elusive. The SELEX technology was used to identify aptamers that specifically recognize DDP‐resistant lung cancer cells and couple them with nano‐zinc (zinc hydroxide, Zn(OH)2) carriers. USP14 levels were higher in DDP‐resistant lung cancer compared to DDP‐sensitive lung cancer. The survival rate of lung cancer patients with increased USP14 expression was significantly lower than the survival rate of patients with low USP14 expression. Silencing USP14 increased the tumor antagonistic action of DDP in A549 cisplatin‐resistant (A549/DDP) cells, while USP14 overexpression decreased the antagonist effects. Aptamer‐targeted nano‐zinc carriers were loaded with USP14 siRNA to target DDP‐resistant lung cancer cells. Aptamer‐targeted nano‐zinc carriers containing USP14 siRNA increased the antitumor effects of DDP in A549/DDP cells and mice bearing A549/DDP cells. These results indicate that aptamer‐guided nano‐zinc carriers may be a potent carrier for the precise treatment of drug‐resistant tumors.
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publishDate 2023-04-01
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spelling doaj-art-bc775a4328ff42739899a780b53d99252025-01-24T05:36:29ZengWileyMedComm2688-26632023-04-0142n/an/a10.1002/mco2.237Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNAXinmin Zhao0Xianghua Wu1Huijie Wang2Songtao Lai3Jialei Wang4Department of Thoracic Medical Oncology Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Thoracic Medical Oncology Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Thoracic Medical Oncology Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Oncology Shanghai Medical College, Fudan University Shanghai ChinaDepartment of Thoracic Medical Oncology Fudan University Shanghai Cancer Center Shanghai ChinaAbstract Cisplatin (DDP) is a common therapeutic option for non‐small cell lung carcinoma (NSCLC). However, some patients fail to respond to the DDP chemotherapy. Therefore, identifying novel biomarkers to improve the diagnosis and treatment of NSCLC is important. Ubiquitin‐specific protease (USP14) is involved in various pathological conditions including cancer; however, the role of USP14 in NSCLC remains elusive. The SELEX technology was used to identify aptamers that specifically recognize DDP‐resistant lung cancer cells and couple them with nano‐zinc (zinc hydroxide, Zn(OH)2) carriers. USP14 levels were higher in DDP‐resistant lung cancer compared to DDP‐sensitive lung cancer. The survival rate of lung cancer patients with increased USP14 expression was significantly lower than the survival rate of patients with low USP14 expression. Silencing USP14 increased the tumor antagonistic action of DDP in A549 cisplatin‐resistant (A549/DDP) cells, while USP14 overexpression decreased the antagonist effects. Aptamer‐targeted nano‐zinc carriers were loaded with USP14 siRNA to target DDP‐resistant lung cancer cells. Aptamer‐targeted nano‐zinc carriers containing USP14 siRNA increased the antitumor effects of DDP in A549/DDP cells and mice bearing A549/DDP cells. These results indicate that aptamer‐guided nano‐zinc carriers may be a potent carrier for the precise treatment of drug‐resistant tumors.https://doi.org/10.1002/mco2.237cisplatin‐resistancenano‐zinc carriersnon‐small cell lung cancersmall interfering RNAtargeted therapy
spellingShingle Xinmin Zhao
Xianghua Wu
Huijie Wang
Songtao Lai
Jialei Wang
Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNA
MedComm
cisplatin‐resistance
nano‐zinc carriers
non‐small cell lung cancer
small interfering RNA
targeted therapy
title Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNA
title_full Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNA
title_fullStr Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNA
title_full_unstemmed Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNA
title_short Targeted therapy for cisplatin‐resistant lung cancer via aptamer‐guided nano‐zinc carriers containing USP14 siRNA
title_sort targeted therapy for cisplatin resistant lung cancer via aptamer guided nano zinc carriers containing usp14 sirna
topic cisplatin‐resistance
nano‐zinc carriers
non‐small cell lung cancer
small interfering RNA
targeted therapy
url https://doi.org/10.1002/mco2.237
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