Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy

Theranostics
Ling LiChangyang Gong

Abstract

Cancer stem cell-like cells (CSCL) are responsible for tumor recurrence associated with conventional therapy (e.g. surgery, radiation, and chemotherapy). Here, we developed a novel multifunctional nucleus-targeting nanoparticle-based gene delivery system which is capable of targeting and eradicating CSCL. These nanoparticles can facilitate efficient endosomal escape and spontaneously penetrate into nucleus without additional nuclear localization signal. They also induced extremely high gene transfection efficiency (>95%) even in culture medium containing 30% serum, which significantly surpassed that of some commercial transfection reagents, such as Lipofectamine 2000 and Lipofectamine 3000 etc. Especially, when loaded with the TRAIL gene, this system mediated remarkable depletion of CSCL. Upon systemic administration, the nanoparticles accumulated in tumor sites while sparing the non-cancer tissues and significantly inhibited the growth of tumors with no evident systemic toxicity. Taken together, our results suggest that these novel multifunctional, nucleus-targeting nanoparticles are a very promising in vivo gene delivery system capable of targeting CSCL and represent a new treatment candidate for improving the survival of can...Continue Reading

Citations

Sep 11, 2019·Nanotoxicology·Nashwa M OsmanImran Y Saleem
Aug 25, 2019·Acta Pharmacologica Sinica·Hui-Hai ZhongYong-Zhuo Huang
Jul 17, 2020·Journal of Drug Targeting·Gizem TezelHakan Eroğlu
Jan 13, 2018·Human Gene Therapy·Li LiuYuquan Wei
Aug 8, 2019·Expert Opinion on Drug Delivery·Yu Sakurai, Hideyoshi Harashima
Sep 28, 2018·Advanced Materials·Wei-Hai ChenXian-Zheng Zhang
Jan 7, 2021·Future Oncology·Deepika SinghGopeshwar Narayan
Mar 10, 2021·Chemical Society Reviews·Jia Lv, Yiyun Cheng
Jul 8, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Reza MohammadinejadAli Zarrabi
Sep 18, 2020·ACS Applied Materials & Interfaces·Xinyu WangYiyun Cheng

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Methods Mentioned

BETA
transfection
dynamic light scattering
flow cytometry
FACS
Xenograft
Fluorescence
xenografts

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