A DNA/Upconversion Nanoparticle Complex Enables Controlled Co-Delivery of CRISPR-Cas9 and Photodynamic Agents for Synergistic Cancer Therapy

© 2024 Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 15 vom: 01. Apr., Seite e2309534
1. Verfasser: Song, Nachuan (VerfasserIn)
Weitere Verfasser: Fan, Xiaoting, Guo, Xiaocui, Tang, Jianpu, Li, Hongjin, Tao, Ruoyu, Li, Fengqin, Li, Junru, Yang, Dayong, Yao, Chi, Liu, Peifeng
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article CRISPR‐Cas9 DNA nanotechnology gene editing photodynamic therapy upconversion nanoparticle Reactive Oxygen Species Antioxidants Hemin 743LRP9S7N mehr... Hydrogen Peroxide BBX060AN9V RNA, Guide, CRISPR-Cas Systems Photosensitizing Agents
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520 |a Photodynamic therapy (PDT) depends on the light-irradiated exciting of photosensitizer (PS) to generate reactive oxygen species (ROS), which faces challenges and limitations in hypoxia and antioxidant response of cancer cells, and limited tissue-penetration of light. Herein, a multifunctional DNA/upconversion nanoparticles (UCNPs) complex is developed which enables controlled co-delivery of CRISPR-Cas9, hemin, and protoporphyrin (PP) for synergistic PDT. An ultralong single-stranded DNA (ssDNA) is prepared via rolling circle amplification (RCA), which contains recognition sequences of single guide RNA (sgRNA) for loading Cas9 ribonucleoprotein (RNP), G-quadruplex sequences for loading hemin and PP, and linker sequences for combining UCNP. Cas9 RNP cleaves the antioxidant regulator nuclear factor E2-related factor 2 (Nrf2), improving the sensitivity of cancer cells to ROS, and enhancing the synergistic PDT effect. The G-quadruplex/hemin DNAzyme mimicks horseradish peroxidase (HRP) to catalyze the endogenous H2O2 to O2, overcoming hypoxia condition in tumors. The introduced UCNP converts NIR irradiation with deep tissue penetration to light with shorter wavelength, exciting PP to transform the abundant O2 to 1O2. The integration of gene editing and PDT allows substantial accumulation of 1O2 in cancer cells for enhanced cell apoptosis, and this synergistic PDT has shown remarkable therapeutic efficacy in a breast cancer mouse model 
650 4 |a Journal Article 
650 4 |a CRISPR‐Cas9 
650 4 |a DNA nanotechnology 
650 4 |a gene editing 
650 4 |a photodynamic therapy 
650 4 |a upconversion nanoparticle 
650 7 |a Reactive Oxygen Species  |2 NLM 
650 7 |a Antioxidants  |2 NLM 
650 7 |a Hemin  |2 NLM 
650 7 |a 743LRP9S7N  |2 NLM 
650 7 |a Hydrogen Peroxide  |2 NLM 
650 7 |a BBX060AN9V  |2 NLM 
650 7 |a RNA, Guide, CRISPR-Cas Systems  |2 NLM 
650 7 |a Photosensitizing Agents  |2 NLM 
700 1 |a Fan, Xiaoting  |e verfasserin  |4 aut 
700 1 |a Guo, Xiaocui  |e verfasserin  |4 aut 
700 1 |a Tang, Jianpu  |e verfasserin  |4 aut 
700 1 |a Li, Hongjin  |e verfasserin  |4 aut 
700 1 |a Tao, Ruoyu  |e verfasserin  |4 aut 
700 1 |a Li, Fengqin  |e verfasserin  |4 aut 
700 1 |a Li, Junru  |e verfasserin  |4 aut 
700 1 |a Yang, Dayong  |e verfasserin  |4 aut 
700 1 |a Yao, Chi  |e verfasserin  |4 aut 
700 1 |a Liu, Peifeng  |e verfasserin  |4 aut 
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773 1 8 |g volume:36  |g year:2024  |g number:15  |g day:01  |g month:04  |g pages:e2309534 
856 4 0 |u http://dx.doi.org/10.1002/adma.202309534  |3 Volltext 
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