Covalent Organic Framework Embedded with Magnetic Nanoparticles for MRI and Chemo-Thermotherapy

Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly­(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy...

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Published inJournal of the American Chemical Society Vol. 142; no. 44; pp. 18782 - 18794
Main Authors Benyettou, Farah, Das, Gobinda, Nair, Anjana Ramdas, Prakasam, Thirumurugan, Shinde, Digambar B, Sharma, Sudhir Kumar, Whelan, Jamie, Lalatonne, Yoann, Traboulsi, Hassan, Pasricha, Renu, Abdullah, Osama, Jagannathan, Ramesh, Lai, Zhiping, Motte, Laurence, Gándara, Felipe, Sadler, Kirsten C, Trabolsi, Ali
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 04.11.2020
Subjects
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
aqueous solutions
Cell Line, Tumor
Cell Survival - drug effects
cytotoxicity
Danio rerio
doxorubicin
Doxorubicin - chemistry
Doxorubicin - metabolism
Doxorubicin - pharmacology
Drug Carriers - chemistry
Embryo, Nonmammalian - drug effects
endosomes
Ferric Compounds - chemistry
fever
glioblastoma
heat transfer
HEK293 Cells
Humans
Hydrogen-Ion Concentration
Hyperthermia, Induced
Imines - chemistry
lysine
lysosomes
magnetic fields
Magnetic Resonance Imaging
Magnetite Nanoparticles - chemistry
Nanoparticles - chemistry
Polylysine - chemistry
polymers
Porosity
Temperature
Zebrafish - growth & development
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Abstract Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly­(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.
AbstractList Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.
Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe₂O₃ NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.
Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly­(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.
Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe O NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.
Author Gándara, Felipe
Trabolsi, Ali
Nair, Anjana Ramdas
Das, Gobinda
Sadler, Kirsten C
Shinde, Digambar B
Jagannathan, Ramesh
Lalatonne, Yoann
Abdullah, Osama
Pasricha, Renu
Lai, Zhiping
Motte, Laurence
Prakasam, Thirumurugan
Sharma, Sudhir Kumar
Traboulsi, Hassan
Whelan, Jamie
Benyettou, Farah
AuthorAffiliation Inserm, U1148, Laboratory for Vascular Translational Science
Services de Biochimie et Médecine Nucléaire
Laboratory for Vascular Translational Science, LVTS, INSERM, UMR 1148
Hôpital Avicenne Assistance Publique-Hôpitaux de Paris
Advanced Membranes and Porous Materials Center, Division of Physical Science and Engineering
Université Sorbonne Paris Nord, Sorbonne Paris Cité
Department of Chemistry, College of Science
Université Sorbonne Paris Nord
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33090806$$D View this record in MEDLINE/PubMed
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Snippet Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide...
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SubjectTerms Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
aqueous solutions
Cell Line, Tumor
Cell Survival - drug effects
cytotoxicity
Danio rerio
doxorubicin
Doxorubicin - chemistry
Doxorubicin - metabolism
Doxorubicin - pharmacology
Drug Carriers - chemistry
Embryo, Nonmammalian - drug effects
endosomes
Ferric Compounds - chemistry
fever
glioblastoma
heat transfer
HEK293 Cells
Humans
Hydrogen-Ion Concentration
Hyperthermia, Induced
Imines - chemistry
lysine
lysosomes
magnetic fields
Magnetic Resonance Imaging
Magnetite Nanoparticles - chemistry
Nanoparticles - chemistry
Polylysine - chemistry
polymers
Porosity
Temperature
Zebrafish - growth & development
Title Covalent Organic Framework Embedded with Magnetic Nanoparticles for MRI and Chemo-Thermotherapy
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