Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells

Chemo and siRNA synergic treatments for tumors is a promising new therapeutic trend. Selenocystine, a selenium analog of cysteine, has been considered a potential antitumor agent due to its redox perturbing role. In this study, we developed a nanocarrier for siRNA based on a selenocystine analog eng...

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Main Authors: Yang Liu, Haoying Yang, Qian Liu, Mingming Pan, Danli Wang, Shiyuan Pan, Weiran Zhang, Jinfeng Wei, Xiaowei Zhao, Junfeng Ji
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/4/1302
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author Yang Liu
Haoying Yang
Qian Liu
Mingming Pan
Danli Wang
Shiyuan Pan
Weiran Zhang
Jinfeng Wei
Xiaowei Zhao
Junfeng Ji
author_facet Yang Liu
Haoying Yang
Qian Liu
Mingming Pan
Danli Wang
Shiyuan Pan
Weiran Zhang
Jinfeng Wei
Xiaowei Zhao
Junfeng Ji
author_sort Yang Liu
collection DOAJ
description Chemo and siRNA synergic treatments for tumors is a promising new therapeutic trend. Selenocystine, a selenium analog of cysteine, has been considered a potential antitumor agent due to its redox perturbing role. In this study, we developed a nanocarrier for siRNA based on a selenocystine analog engineered polyetherimide and achieved traceable siRNA delivery and the synergic killing of tumor cells. Notably, we applied the label-free Schiff base fluorescence mechanism, which enabled us to trace the siRNA delivery and to monitor the selenocystine analogs’ local performance. A novel selenocystine-derived fluorescent Schiff base linker was used to crosslink the polyetherimide, thereby generating a traceable siRNA delivery vehicle with green fluorescence. Moreover, we found that this compound induced tumor cells to undergo senescence. Together with the delivery of a siRNA targeting the anti-apoptotic <i>BCL-xl/w</i> genes in senescent cells, it achieved a synergistic inhibition function by inducing both senescence and apoptosis of tumor cells. Therefore, this study provides insights into the development of label-free probes, prodrugs, and materials towards the synergic strategies for cancer therapy.
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spelling doaj.art-b23c223000284f4589b737f065c6bde02023-11-23T21:21:52ZengMDPI AGMolecules1420-30492022-02-01274130210.3390/molecules27041302Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer CellsYang Liu0Haoying Yang1Qian Liu2Mingming Pan3Danli Wang4Shiyuan Pan5Weiran Zhang6Jinfeng Wei7Xiaowei Zhao8Junfeng Ji9Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaHenan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng 475004, ChinaHenan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng 475004, ChinaHenan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng 475004, ChinaZhoushan Hospital of Zhejiang Province, Zhoushan 316004, ChinaHenan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng 475004, ChinaHenan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng 475004, ChinaHenan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng 475004, ChinaHenan Key Laboratory of Brain Targeted Bio-Nanomedicine, School of Life Sciences & School of Pharmacy, Henan University, Kaifeng 475004, ChinaCenter of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou 310058, ChinaChemo and siRNA synergic treatments for tumors is a promising new therapeutic trend. Selenocystine, a selenium analog of cysteine, has been considered a potential antitumor agent due to its redox perturbing role. In this study, we developed a nanocarrier for siRNA based on a selenocystine analog engineered polyetherimide and achieved traceable siRNA delivery and the synergic killing of tumor cells. Notably, we applied the label-free Schiff base fluorescence mechanism, which enabled us to trace the siRNA delivery and to monitor the selenocystine analogs’ local performance. A novel selenocystine-derived fluorescent Schiff base linker was used to crosslink the polyetherimide, thereby generating a traceable siRNA delivery vehicle with green fluorescence. Moreover, we found that this compound induced tumor cells to undergo senescence. Together with the delivery of a siRNA targeting the anti-apoptotic <i>BCL-xl/w</i> genes in senescent cells, it achieved a synergistic inhibition function by inducing both senescence and apoptosis of tumor cells. Therefore, this study provides insights into the development of label-free probes, prodrugs, and materials towards the synergic strategies for cancer therapy.https://www.mdpi.com/1420-3049/27/4/1302selenocystinefluorescent Schiff baseSchiff base probesiRNA nanoparticletumor senescence
spellingShingle Yang Liu
Haoying Yang
Qian Liu
Mingming Pan
Danli Wang
Shiyuan Pan
Weiran Zhang
Jinfeng Wei
Xiaowei Zhao
Junfeng Ji
Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells
Molecules
selenocystine
fluorescent Schiff base
Schiff base probe
siRNA nanoparticle
tumor senescence
title Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells
title_full Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells
title_fullStr Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells
title_full_unstemmed Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells
title_short Selenocystine-Derived Label-Free Fluorescent Schiff Base Nanocomplex for siRNA Delivery Synergistically Kills Cancer Cells
title_sort selenocystine derived label free fluorescent schiff base nanocomplex for sirna delivery synergistically kills cancer cells
topic selenocystine
fluorescent Schiff base
Schiff base probe
siRNA nanoparticle
tumor senescence
url https://www.mdpi.com/1420-3049/27/4/1302
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