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      miRNA-Guided Imaging and Photodynamic Therapy Treatment of Cancer Cells Using Zn(II)-Protoporphyrin IX-Loaded Metal–Organic Framework Nanoparticles

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          Abstract

          An analytical platform for the selective miRNA-21-guided imaging of breast cancer cells and miRNA-221-guided imaging of ovarian cancer cells and the selective photodynamic therapy (PDT) of these cancer cells is introduced. The method is based on Zn(II)-protoporphyrin IX, Zn(II)-PPIX-loaded UiO-66 metal–organic framework nanoparticles, NMOFs, gated by two hairpins H i/H j through ligation of their phosphate residues to the vacant Zr 4+-ions associated with the NMOFs. The hairpins are engineered to include the miRNA recognition sequence in the stem domain of H i, and in the H i and H j, partial locked stem regions of G-quadruplex subunits. Intracellular phosphate-ions displace the hairpins, resulting in the release of the Zn(II)-PPIX and intracellular miRNAs open H i, and this triggers the autonomous cross-opening of H i and H j. This activates the interhairpin hybridization chain reaction and leads to the assembly of highly fluorescent Zn(II)-PPIX-loaded G-quadruplex chains. The miRNA-guided fluorescent chains allow selective imaging of cancer cells. Moreover, PDT with visible light selectively kills cancer cells and tumor cells through the formation of toxic reactive oxygen species.

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          MicroRNAs: target recognition and regulatory functions.

          MicroRNAs (miRNAs) are endogenous approximately 23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.
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            Metal-organic frameworks in biomedicine.

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              MicroRNA signatures in human cancers.

              MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
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                Author and article information

                Journal
                ACS Nano
                ACS Nano
                nn
                ancac3
                ACS Nano
                American Chemical Society
                1936-0851
                1936-086X
                12 January 2022
                22 February 2022
                : 16
                : 2
                : 1791-1801
                Affiliations
                []Institute of Chemistry, Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel
                []Institute of Life Science, The Hebrew University of Jerusalem , Jerusalem 91904, Israel
                [§ ]The Lautenberg Center for Immunology and Cancer Research, IMRIC, The Hebrew University of Jerusalem , Jerusalem 91120, Israel
                Author notes
                Author information
                https://orcid.org/0000-0001-9710-9077
                Article
                10.1021/acsnano.1c04681
                8867907
                35020370
                f22e9f16-7602-410c-a45e-6f88e1fd3b26
                © 2022 The Authors. Published by American Chemical Society

                Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 02 June 2021
                : 06 January 2022
                Funding
                Funded by: Hebrew University of Jerusalem, doi 10.13039/501100003483;
                Award ID: NA
                Funded by: Minerva Center for Biohybrid Complex Systems, doi NA;
                Award ID: NA
                Funded by: ISF-precision medicine program, doi NA;
                Award ID: NA
                Funded by: Ministry of Science and Technology, Israel, doi 10.13039/501100006245;
                Award ID: NA
                Funded by: Shanghai Jiao Tong University, doi 10.13039/501100004921;
                Award ID: NA
                Categories
                Article
                Custom metadata
                nn1c04681
                nn1c04681

                Nanotechnology
                fluorescence,g-quadruplexes,hybridization chain reaction,breast cancer,ovarian cancer,reactive oxygen species

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