Delivery of Cas13a/crRNA by self-degradable black phosphorus nanosheets to specifically inhibit Mcl-1 for breast cancer therapy.

Journal of Materials Chemistry. B, Materials for Biology and Medicine
Huahua YueDa Xing

Abstract

Mcl-1 amplification has been observed in breast cancer and demonstrated as a key determinant of breast cancer cell survival. However, the clinical use of available effective Mcl-1-specific inhibitors for breast cancer treatment remains a challenge. An RNA-guided CRISPR/Cas13a system targeting RNAs can be used to specifically knock down mRNA expression in mammalian cells. The goal of this work is to develop a self-degradable nanoplatform based on polylysine (PLL)-functionalized black phosphorus (PBP) for the delivery of Cas13a/crRNA complexes to specifically inhibit Mcl-1 at transcriptional level for breast cancer therapy. The constructed Cas13a/crRNA complex is delivered into the cytoplasm by PBP via endocytosis, followed by endosomal escape based on the biodegradation of PBP, and this efficiently knocks down the specific gene at transcriptional level up to an efficiency of 58.64%. Through designing CRISPR RNA crMcl-1, Mcl-1 can be specifically knocked down at transcriptional level in breast cancer cells, resulting in the down-regulation of the expression of Mcl-1 protein and inhibition of the cell activity. Notably, PBP/Cas13a/crMcl-1 shows an excellent tumor suppression efficacy up to 65.16% after intratumoral injection. Ther...Continue Reading

References

May 20, 2003·Nature Biotechnology·Aimee L JacksonPeter S Linsley
Nov 13, 2004·Breast Cancer Research : BCR·Freddie BrayD Maxwell Parkin
Aug 8, 2006·Nature Medicine·Patricia S Steeg
Dec 22, 2007·Nature Reviews. Molecular Cell Biology·Richard J Youle, Andreas Strasser
Jun 4, 2008·Nature Reviews. Genetics·Michael Boutros, Julie Ahringer
Sep 22, 2010·Cancer Biology & Therapy·Clint MitchellPaul Dent
Nov 10, 2010·Breast Cancer Research : BCR·Edgardo Rivera, Henry Gomez
Mar 26, 2011·Science·Christine L Chaffer, Robert A Weinberg
Jan 31, 2013·Nature Biotechnology·Woong Y HwangJ Keith Joung
Oct 1, 2013·Nature Methods·Prashant MaliGeorge M Church
May 21, 2014·Nature Reviews. Genetics·Melissa A Kotterman, David V Schaffer
Mar 19, 2015·ACS Nano·Joohoon KangMark C Hersam
Sep 8, 2015·Nature Methods·Samira KianiGeorge Church
Dec 17, 2015·Nature Reviews. Molecular Cell Biology·Antonia A DominguezLei S Qi
Mar 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Ming WangQiaobing Xu
Mar 22, 2016·Cell·David A NellesGene W Yeo
Sep 27, 2016·Nature·Alexandra East-SeletskyJennifer A Doudna
Apr 15, 2017·Science·Jonathan S GootenbergFeng Zhang
May 6, 2017·Molecular Cell·Alexandra East-SeletskyJennifer A Doudna
Oct 5, 2017·Nature·Omar O AbudayyehFeng Zhang
Oct 27, 2017·Science·David B T CoxFeng Zhang
Dec 12, 2017·The Journal of Clinical Investigation·Guo ChenXingming Deng
Dec 23, 2017·Journal of the American Chemical Society·Shahad K AlsaiariNiveen M Khashab
Jan 4, 2018·Proceedings of the National Academy of Sciences of the United States of America·Meng QiuYihai Cao
Jan 13, 2018·Angewandte Chemie·Malthe Hansen-BruhnJoseph Wang
Jan 18, 2018·Proceedings of the National Academy of Sciences of the United States of America·Raheleh Rezaei AraghiAmy E Keating
Jan 18, 2018·Cell Death & Disease·Kirsteen J CampbellKaren Blyth
Feb 6, 2018·Analytical Chemistry·Yun ZhaoYong Chen
Feb 22, 2018·Theranostics·Jane Ru ChoiXiaonan Lu
Mar 13, 2018·Chemical Communications : Chem Comm·Huimeng WangHuang-Hao Yang
Mar 27, 2018·Journal of the American Chemical Society·Taiming ZhangLijun Wan
Apr 2, 2018·Trends in Plant Science·Zahir AliMagdy Mahfouz
Apr 28, 2018·Science·Cameron MyhrvoldPardis C Sabeti

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Citations

Jul 30, 2021·Advanced Materials·Ye ZhangHan Zhang

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Methods Mentioned

BETA
transmission electron microscopy
atomic force microscopy
dynamic-light-scattering
X-ray
infrared spectroscopy
Fluorescence
in vitro transcription
electrophoresis
fluorescence assay
Raman spectroscopy

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