Dual-Locking Nanoparticles Disrupt the PD-1/PD-L1 Pathway for Efficient Cancer Immunotherapy

Dual-Locking Nanoparticles Disrupt the PD-1/PD-L1 Pathway for Efficient Cancer Immunotherapy

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 31(2019), 51 vom: 25. Dez., Seite e1905751
1. Verfasser: Zhang, Zhanzhan (VerfasserIn)
Weitere Verfasser: Wang, Qixue, Liu, Qi, Zheng, Yadan, Zheng, Chunxiong, Yi, Kaikai, Zhao, Yu, Gu, Yu, Wang, Ying, Wang, Chun, Zhao, Xinzhi, Shi, Linqi, Kang, Chunsheng, Liu, Yang
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article CRISPR/Cas13a Cas13a/PD-L1 cancer immunotherapy collateral effect dual-locking nanoparticles B7-H1 Antigen CRISPR-Associated Proteins Cd274 protein, mouse Programmed Cell Death 1 Receptor mehr... Polyethylene Glycols 3WJQ0SDW1A Hydrogen Peroxide BBX060AN9V
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500 |a Date Completed 30.04.2020 
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500 |a Citation Status MEDLINE 
520 |a © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 
520 |a The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) enzyme, Cas13a, holds great promise in cancer treatment due to its potential for selective destruction of tumor cells via collateral effects after target recognition. However, these collateral effects do not specifically target tumor cells and may cause safety issues when administered systemically. Herein, a dual-locking nanoparticle (DLNP) that can restrict CRISPR/Cas13a activation to tumor tissues is described. DLNP has a core-shell structure, in which the CRISPR/Cas13a system (plasmid DNA, pDNA) is encapsulated inside the core with a dual-responsive polymer layer. This polymer layer endows the DLNP with enhanced stability during blood circulation or in normal tissues and facilitates cellular internalization of the CRISPR/Cas13a system and activation of gene editing upon entry into tumor tissue. After carefully screening and optimizing the CRISPR RNA (crRNA) sequence that targets programmed death-ligand 1 (PD-L1), DLNP demonstrates the effective activation of T-cell-mediated antitumor immunity and the reshaping of immunosuppressive tumor microenvironment (TME) in B16F10-bearing mice, resulting in significantly enhanced antitumor effect and improved survival rate. Further development by replacing the specific crRNA of target genes can potentially make DLNP a universal platform for the rapid development of safe and efficient cancer immunotherapies 
650 4 |a Journal Article 
650 4 |a CRISPR/Cas13a 
650 4 |a Cas13a/PD-L1 
650 4 |a cancer immunotherapy 
650 4 |a collateral effect 
650 4 |a dual-locking nanoparticles 
650 7 |a B7-H1 Antigen  |2 NLM 
650 7 |a CRISPR-Associated Proteins  |2 NLM 
650 7 |a Cd274 protein, mouse  |2 NLM 
650 7 |a Programmed Cell Death 1 Receptor  |2 NLM 
650 7 |a Polyethylene Glycols  |2 NLM 
650 7 |a 3WJQ0SDW1A  |2 NLM 
650 7 |a Hydrogen Peroxide  |2 NLM 
650 7 |a BBX060AN9V  |2 NLM 
700 1 |a Wang, Qixue  |e verfasserin  |4 aut 
700 1 |a Liu, Qi  |e verfasserin  |4 aut 
700 1 |a Zheng, Yadan  |e verfasserin  |4 aut 
700 1 |a Zheng, Chunxiong  |e verfasserin  |4 aut 
700 1 |a Yi, Kaikai  |e verfasserin  |4 aut 
700 1 |a Zhao, Yu  |e verfasserin  |4 aut 
700 1 |a Gu, Yu  |e verfasserin  |4 aut 
700 1 |a Wang, Ying  |e verfasserin  |4 aut 
700 1 |a Wang, Chun  |e verfasserin  |4 aut 
700 1 |a Zhao, Xinzhi  |e verfasserin  |4 aut 
700 1 |a Shi, Linqi  |e verfasserin  |4 aut 
700 1 |a Kang, Chunsheng  |e verfasserin  |4 aut 
700 1 |a Liu, Yang  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Advanced materials (Deerfield Beach, Fla.)  |d 1998  |g 31(2019), 51 vom: 25. Dez., Seite e1905751  |w (DE-627)NLM098206397  |x 1521-4095  |7 nnas 
773 1 8 |g volume:31  |g year:2019  |g number:51  |g day:25  |g month:12  |g pages:e1905751 
856 4 0 |u http://dx.doi.org/10.1002/adma.201905751  |3 Volltext 
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