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Tailored Lipoprotein‐Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor‐Stimulated Macropinocytosis

Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by...

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Detalles Bibliográficos
Autores principales: Jiang, Gan, Chen, Huan, Huang, Jialin, Song, Qingxiang, Chen, Yaoxing, Gu, Xiao, Jiang, Zhenhuan, Huang, Yukun, Lin, Yingying, Feng, Junfeng, Jiang, Jiyao, Bao, Yinghui, Zheng, Gang, Chen, Jun, Chen, Hongzhuan, Gao, Xiaoling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055550/
https://www.ncbi.nlm.nih.gov/pubmed/32154087
http://dx.doi.org/10.1002/advs.201903290
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author Jiang, Gan
Chen, Huan
Huang, Jialin
Song, Qingxiang
Chen, Yaoxing
Gu, Xiao
Jiang, Zhenhuan
Huang, Yukun
Lin, Yingying
Feng, Junfeng
Jiang, Jiyao
Bao, Yinghui
Zheng, Gang
Chen, Jun
Chen, Hongzhuan
Gao, Xiaoling
author_facet Jiang, Gan
Chen, Huan
Huang, Jialin
Song, Qingxiang
Chen, Yaoxing
Gu, Xiao
Jiang, Zhenhuan
Huang, Yukun
Lin, Yingying
Feng, Junfeng
Jiang, Jiyao
Bao, Yinghui
Zheng, Gang
Chen, Jun
Chen, Hongzhuan
Gao, Xiaoling
author_sort Jiang, Gan
collection PubMed
description Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by the metabolic difference in endocytosis between GICs, differentiated glioma cells, and normal cells, a tailored lipoprotein‐like nanostructure is developed to amplify their internalization into GICs through receptor‐stimulated macropinocytosis. As CXCR4 is highly expressed on GICs and glioma tumor sites, meanwhile, the activation of CXCR4 induces the receptor‐stimulated macropinocytosis pathway in GICs, this CXCR4 receptor‐stimulated lipoprotein‐like nanoparticle (SLNP) achieves efficient accumulation in GICs in vitro and in vivo. By carrying microRNA‐34a in the core, this tailored SLNP reduces sex‐determining region Y‐box 2 and Notch1 expression, powerfully inhibits GICs stemness and chemoresistance, and significantly prolongs the survival of GICs‐bearing mice. Taken together, a tailored lipoprotein‐based nanostructure realizes efficient GICs accumulation and therapeutic effect through receptor‐stimulated macropinocytosis, providing a powerful nanoplatform for RNA interference drugs to combat glioma.
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spelling pubmed-70555502020-03-09 Tailored Lipoprotein‐Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor‐Stimulated Macropinocytosis Jiang, Gan Chen, Huan Huang, Jialin Song, Qingxiang Chen, Yaoxing Gu, Xiao Jiang, Zhenhuan Huang, Yukun Lin, Yingying Feng, Junfeng Jiang, Jiyao Bao, Yinghui Zheng, Gang Chen, Jun Chen, Hongzhuan Gao, Xiaoling Adv Sci (Weinh) Full Papers Glioma initiating cells (GICs) function as the seed for the propagation and relapse of glioma. Designing a smart and efficient strategy to target the GICs and to suppress the multiple signaling pathways associated with stemness and chemoresistance is essential to achieving a cancer cure. Inspired by the metabolic difference in endocytosis between GICs, differentiated glioma cells, and normal cells, a tailored lipoprotein‐like nanostructure is developed to amplify their internalization into GICs through receptor‐stimulated macropinocytosis. As CXCR4 is highly expressed on GICs and glioma tumor sites, meanwhile, the activation of CXCR4 induces the receptor‐stimulated macropinocytosis pathway in GICs, this CXCR4 receptor‐stimulated lipoprotein‐like nanoparticle (SLNP) achieves efficient accumulation in GICs in vitro and in vivo. By carrying microRNA‐34a in the core, this tailored SLNP reduces sex‐determining region Y‐box 2 and Notch1 expression, powerfully inhibits GICs stemness and chemoresistance, and significantly prolongs the survival of GICs‐bearing mice. Taken together, a tailored lipoprotein‐based nanostructure realizes efficient GICs accumulation and therapeutic effect through receptor‐stimulated macropinocytosis, providing a powerful nanoplatform for RNA interference drugs to combat glioma. John Wiley and Sons Inc. 2020-01-20 /pmc/articles/PMC7055550/ /pubmed/32154087 http://dx.doi.org/10.1002/advs.201903290 Text en © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Jiang, Gan
Chen, Huan
Huang, Jialin
Song, Qingxiang
Chen, Yaoxing
Gu, Xiao
Jiang, Zhenhuan
Huang, Yukun
Lin, Yingying
Feng, Junfeng
Jiang, Jiyao
Bao, Yinghui
Zheng, Gang
Chen, Jun
Chen, Hongzhuan
Gao, Xiaoling
Tailored Lipoprotein‐Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor‐Stimulated Macropinocytosis
title Tailored Lipoprotein‐Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor‐Stimulated Macropinocytosis
title_full Tailored Lipoprotein‐Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor‐Stimulated Macropinocytosis
title_fullStr Tailored Lipoprotein‐Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor‐Stimulated Macropinocytosis
title_full_unstemmed Tailored Lipoprotein‐Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor‐Stimulated Macropinocytosis
title_short Tailored Lipoprotein‐Like miRNA Delivery Nanostructure Suppresses Glioma Stemness and Drug Resistance through Receptor‐Stimulated Macropinocytosis
title_sort tailored lipoprotein‐like mirna delivery nanostructure suppresses glioma stemness and drug resistance through receptor‐stimulated macropinocytosis
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055550/
https://www.ncbi.nlm.nih.gov/pubmed/32154087
http://dx.doi.org/10.1002/advs.201903290
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