Controllable Star Cationic Poly(Disulfide)s Achieve Genetically Cascade Catalytic Therapy by Delivering Bifunctional Fusion Plasmids

© 2023 Wiley-VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 35(2023), 52 vom: 01. Dez., Seite e2307190
1. Verfasser: Yu, Dan (VerfasserIn)
Weitere Verfasser: Wang, Yuanchen, Qu, Shuang, Zhang, Na, Nie, Kaili, Wang, Junkai, Huang, Yichun, Sui, Dandan, Yu, Bingran, Qin, Meng, Xu, Fu-Jian
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article cascade therapy caveolae-mediated pathway controllable disulfide exchange polymerization fusion plasmid tumor hypoxia modulation Disulfides Reactive Oxygen Species
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520 |a The absence of effective delivery vectors and suitable multifunctional plasmids limits cancer gene therapy development. The star cationic poly(disulfide)s with β-cyclodextrin cores (termed β-CD-g-PSSn ) for caveolae-mediated endocytosis are designed and prepared via mild and controllable disulfide exchange polymerization for high-efficacy cancer therapy. Then, β-CD-g-PSSn /pDNA complexes are transported to the Golgi apparatus and endoplasmic reticulum. Disulfides in β-CD-g-PSSn vectors are degraded by glutathione in tumor cells, which not only promotes intracellular pDNA release but also reduces in vitro and in vivo toxicity. One bifunctional fusion plasmid pCATKR, which expresses catalase (CAT) fused to KillerRed (KR) (CATKR) in the same target cell, is also proposed for genetically cascade catalytic therapy. When compared with pCAT-KR (plasmid expressing CAT and KR separately in the same cell), delivered pCATKR decomposes hydrogen peroxide, alleviates tumor hypoxia more effectively, generates stronger reactive oxygen species (ROS) capabilities under moderate irradiation, and leads to robust antitumor cascade photodynamic effects. These impressive results are attributed to fusion protein design, which shortens the distance between CAT and KR catalytic centers and leads to improved ROS production efficiency. This work provides a promising strategy by delivering a catalytic cascade functional plasmid via a high-performance vector with biodegradable and caveolae-mediated endocytosis characteristics 
650 4 |a Journal Article 
650 4 |a cascade therapy 
650 4 |a caveolae-mediated pathway 
650 4 |a controllable disulfide exchange polymerization 
650 4 |a fusion plasmid 
650 4 |a tumor hypoxia modulation 
650 7 |a Disulfides  |2 NLM 
650 7 |a Reactive Oxygen Species  |2 NLM 
700 1 |a Wang, Yuanchen  |e verfasserin  |4 aut 
700 1 |a Qu, Shuang  |e verfasserin  |4 aut 
700 1 |a Zhang, Na  |e verfasserin  |4 aut 
700 1 |a Nie, Kaili  |e verfasserin  |4 aut 
700 1 |a Wang, Junkai  |e verfasserin  |4 aut 
700 1 |a Huang, Yichun  |e verfasserin  |4 aut 
700 1 |a Sui, Dandan  |e verfasserin  |4 aut 
700 1 |a Yu, Bingran  |e verfasserin  |4 aut 
700 1 |a Qin, Meng  |e verfasserin  |4 aut 
700 1 |a Xu, Fu-Jian  |e verfasserin  |4 aut 
773 0 8 |i Enthalten in  |t Advanced materials (Deerfield Beach, Fla.)  |d 1998  |g 35(2023), 52 vom: 01. Dez., Seite e2307190  |w (DE-627)NLM098206397  |x 1521-4095  |7 nnns 
773 1 8 |g volume:35  |g year:2023  |g number:52  |g day:01  |g month:12  |g pages:e2307190 
856 4 0 |u http://dx.doi.org/10.1002/adma.202307190  |3 Volltext 
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