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Title:
Targeted OUM1/PTPRZ1 silencing and synergetic CDT/enhanced chemical therapy toward uveal melanoma based on a dual-modal imaging-guided manganese metalāorganic framework nanoparticles | Journal of Nanobiotechnology
Description:
Metastasis and chemical resistance are the most serious problems in the treatment of highly aggressive uveal melanoma (UM). The newly identified lncRNA OUM1 is overexpressed in UM, functions as a catalyst and regulates protein tyrosine phosphatase (PTP) activity by binding to PTP receptor type Z1 (PTPRZ1), which plays an important role in cell proliferation, metastasis and chemotherapy resistance in the UM microenvironment. Hence, siRNAs that selectively knocking down the lncRNA OUM1 (siOUM1) and its target gene PTPRZ1 (siPTPRZ1) were designed to inhibit the OUM1/PTPRZ1 pathway to reduce PTP activity, and this reduction in activity interrupts protein tyrosine phosphorylation, suppresses UM proliferation and metastasis and improves cisplatin sensitivity in UM cells. Then, to overcome the limitations of the difficulty of drug administration and traditional therapeutics, the indocyanine green (ICG)-labeled manganese metalāorganic framework (MOF) nanoparticles (NPs) were fabricated and linked with arginine-glycine-aspartate (RGD) peptide to carry siOUM1/siPTPRZ1 and cisplatin to achieve targeted siRNA interference-mediated therapy, enhanced cisplatin therapy and chemodynamic therapy. This NP system also has a dual-modal imaging ability because ICG is a near-infrared region fluorescent dye and manganese has the potential to be used in magnetic resonance imaging. This study verifies the significance of the newly discovered lncRNA OUM1 as a new therapeutic target for aggressive UM and provides a drug delivery NP system for precise treatment of UM accompanied with a dual-modal imaging ability. Graphical Abstract
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Keywords {š}
cells, oum, fig, nps, ptprz, tumor, article, pubmed, expression, ocma, google, scholar, cell, icgcopmofpr, metastasis, protein, mof, mice, melanoma, cisplatin, cas, rna, therapy, imaging, knockdown, activity, drug, shoumocma, analysis, ptp, effect, additional, siptprz, vivo, significantly, file, study, shanghai, proliferation, cancer, lncrnas, tissues, injected, assay, data, nanoparticles, zhang, tyrosine, system, detected,
Topics {āļø}
hollow metal-organic-framework micro/nanostructures cross-linked alginate/pectin hydrogel metal-organic framework nanoparticles fluorescence/mri dual-modal imaging metalāorganic framework nps dual-modal imaging ability dual-modal imaging capacity metal-organic frameworks metalāorganic frameworks time-dependent t1-weighted enhancement metal-organic framework carboxyl-peg-nh2 aqueous solution metal-polyphenol-coordinated nanomedicine effective oligonucleotide-delivery systems 15 µgĀ mlā1 icg-mof-pr metal-based nanomaterials combine rna interference-mediated therapy sirna interference-mediated therapy n2 absorptionāāādesorption isotherm synthesize double-stranded cdnas article download pdf triple-negative breast cancer based drug/cargo delivery activating pi3k/akt signaling 4Ā pmol po4/min/μg 5Ā pmol po4/min/μg 0Ā pmol po4/min/μg 9Ā pmol po4/min/μg 2Ā pmol po4/min/μg 7Ā pmol po4/min/μg 1Ā pmol po4/min/μg 6Ā pmol po4/min/μg 8Ā pmol po4/min/μg nu/nu nude mice ph-responsive drug delivery genome-wide cdna array paraffin-fluorescence probe-fish dose-dependent cell viability fluorescein-labeled negative control icg-cis-loaded nps arginine-glycine-aspartate nir dual imaging ability mof-pr showed ca ros-responsive tk linkers uveal melanoma based molybdate dye/additive mixture ocm1a-tumor-bearing balb/ protein tyrosine phosphorylation drug delivery nanoparticles posterior uveal melanoma
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headline:Targeted OUM1/PTPRZ1 silencing and synergetic CDT/enhanced chemical therapy toward uveal melanoma based on a dual-modal imaging-guided manganese metalāorganic framework nanoparticles
description:Metastasis and chemical resistance are the most serious problems in the treatment of highly aggressive uveal melanoma (UM). The newly identified lncRNA OUM1 is overexpressed in UM, functions as a catalyst and regulates protein tyrosine phosphatase (PTP) activity by binding to PTP receptor type Z1 (PTPRZ1), which plays an important role in cell proliferation, metastasis and chemotherapy resistance in the UM microenvironment. Hence, siRNAs that selectively knocking down the lncRNA OUM1 (siOUM1) and its target gene PTPRZ1 (siPTPRZ1) were designed to inhibit the OUM1/PTPRZ1 pathway to reduce PTP activity, and this reduction in activity interrupts protein tyrosine phosphorylation, suppresses UM proliferation and metastasis and improves cisplatin sensitivity in UM cells. Then, to overcome the limitations of the difficulty of drug administration and traditional therapeutics, the indocyanine green (ICG)-labeled manganese metalāorganic framework (MOF) nanoparticles (NPs) were fabricated and linked with arginine-glycine-aspartate (RGD) peptide to carry siOUM1/siPTPRZ1 and cisplatin to achieve targeted siRNA interference-mediated therapy, enhanced cisplatin therapy and chemodynamic therapy. This NP system also has a dual-modal imaging ability because ICG is a near-infrared region fluorescent dye and manganese has the potential to be used in magnetic resonance imaging. This study verifies the significance of the newly discovered lncRNA OUM1 as a new therapeutic target for aggressive UM and provides a drug delivery NP system for precise treatment of UM accompanied with a dual-modal imaging ability.
datePublished:2022-11-05T00:00:00Z
dateModified:2022-11-05T00:00:00Z
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Uveal melanoma
LncRNA OUM1
Protein tyrosine phosphorylation
ICG-siOUM1ā+āsiPTPRZ1ā+āCis@MOF-PR
Fenton-like reaction
Magnetic resonance
Biotechnology
Nanotechnology
Molecular Medicine
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headline:Targeted OUM1/PTPRZ1 silencing and synergetic CDT/enhanced chemical therapy toward uveal melanoma based on a dual-modal imaging-guided manganese metalāorganic framework nanoparticles
description:Metastasis and chemical resistance are the most serious problems in the treatment of highly aggressive uveal melanoma (UM). The newly identified lncRNA OUM1 is overexpressed in UM, functions as a catalyst and regulates protein tyrosine phosphatase (PTP) activity by binding to PTP receptor type Z1 (PTPRZ1), which plays an important role in cell proliferation, metastasis and chemotherapy resistance in the UM microenvironment. Hence, siRNAs that selectively knocking down the lncRNA OUM1 (siOUM1) and its target gene PTPRZ1 (siPTPRZ1) were designed to inhibit the OUM1/PTPRZ1 pathway to reduce PTP activity, and this reduction in activity interrupts protein tyrosine phosphorylation, suppresses UM proliferation and metastasis and improves cisplatin sensitivity in UM cells. Then, to overcome the limitations of the difficulty of drug administration and traditional therapeutics, the indocyanine green (ICG)-labeled manganese metalāorganic framework (MOF) nanoparticles (NPs) were fabricated and linked with arginine-glycine-aspartate (RGD) peptide to carry siOUM1/siPTPRZ1 and cisplatin to achieve targeted siRNA interference-mediated therapy, enhanced cisplatin therapy and chemodynamic therapy. This NP system also has a dual-modal imaging ability because ICG is a near-infrared region fluorescent dye and manganese has the potential to be used in magnetic resonance imaging. This study verifies the significance of the newly discovered lncRNA OUM1 as a new therapeutic target for aggressive UM and provides a drug delivery NP system for precise treatment of UM accompanied with a dual-modal imaging ability.
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Uveal melanoma
LncRNA OUM1
Protein tyrosine phosphorylation
ICG-siOUM1ā+āsiPTPRZ1ā+āCis@MOF-PR
Fenton-like reaction
Magnetic resonance
Biotechnology
Nanotechnology
Molecular Medicine
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name:Xueru Liu
affiliation:
name:Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine
address:
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology
address:
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
type:PostalAddress
type:Organization
name:Qinghao Zhang
affiliation:
name:East China University of Science and Technology
address:
name:East China University of Science and Technology, Shanghai, China
type:PostalAddress
type:Organization
name:Caiwen Xiao
affiliation:
name:Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine
address:
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology
address:
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
type:PostalAddress
type:Organization
email:[email protected]
name:He Zhang
affiliation:
name:Tongji University
address:
name:School of Life Science and Technology, Tongji University, Shanghai, China
type:PostalAddress
type:Organization
email:[email protected]
name:Leilei Zhang
affiliation:
name:Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine
address:
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
type:PostalAddress
type:Organization
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology
address:
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:East China University of Science and Technology, Shanghai, China
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:School of Life Science and Technology, Tongji University, Shanghai, China
name:Department of Ophthalmology, Shanghai Ninth Peopleās Hospital Afflicted to Shanghai Jiao Tong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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