Development of a magnetic nano-graphene oxide carrier for improved glioma-targeted drug delivery and imaging: In vitro and in vivo evaluations
To overcome the obstacles inflicted by the BBB in Glioblastoma multiforme (GBM) we investigated the use of Multifunctional nanoparticles that designed with a Nano-graphene oxide (NGO) sheet functionalized with magnetic poly (lactic-co-glycolic acid) (PLGA) and was used for glioma targeting delivery...
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| Veröffentlicht in: | Chemico-biological interactions 2018-11, Vol.295, p.97-108 |
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| creator | Shirvalilou, Sakine Khoei, Samideh Khoee, Sepideh Raoufi, Nida Jamali Karimi, Mohammad Reza Shakeri-Zadeh, Ali |
| description | To overcome the obstacles inflicted by the BBB in Glioblastoma multiforme (GBM) we investigated the use of Multifunctional nanoparticles that designed with a Nano-graphene oxide (NGO) sheet functionalized with magnetic poly (lactic-co-glycolic acid) (PLGA) and was used for glioma targeting delivery of radiosensitizing 5-iodo-2-deoxyuridine (IUdR). In vitro biocompatibility of nanocomposite has been studied by the MTT assay. In vivo efficacy of magnetic targeting on the amount and selectivity of magnetic nanoparticles accumulation in glioma-bearing rats under an external magnetic field (EMF) density of 0.5 T was easily monitored with MRI. IUdR-loaded magnetic NGO/PLGA with a diameter of 71.8 nm, a zeta potential of −33.07 ± 0.07 mV, and a drug loading content of 3.04 ± 0.46% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 15.98 emu/g. Furthermore, Prussian blue staining showed effective magnetic targeting, leading to remarkably improved tumor inhibitory efficiency of IUdR. The tumor volume of rats after treatment with IUdR/NGO/SPION/PLGA + MF was decreased significantly compared to the rats treated with buffer saline, IUdR and SPION/IUdR/NGO/PLGA. Most importantly, our data demonstrate that IUdR/NGO/SPION/PLGA at the present magnetic field prolongs the median survival time of animals bearing gliomas (38 days, p |
| doi_str_mv | 10.1016/j.cbi.2018.08.027 |
| format | Article |
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Schematic illustration of magnetic drug delivery, verified by staining and use as an MRI contrast agent with IUdR/GO/SPION/PLGA and MF. [Display omitted]
•IUdR-loaded magnetic NGO + MF indicated the strongest anticancer effects in rat gliomas.•Magnetic NGO induces thermosensitising effects in alternative magnetic field.•Magnetic NGO under external magnetic field could overcome the BBB.•Magnetic NGO could enhance the MRI sensitivity.•Magnetic NGO modified with PLGA showed sustained release of IUdR.</description><identifier>ISSN: 0009-2797</identifier><identifier>EISSN: 1872-7786</identifier><identifier>DOI: 10.1016/j.cbi.2018.08.027</identifier><identifier>PMID: 30170108</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>5-Iodo-2′-deoxyuridine ; Animals ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Brain Neoplasms - diagnostic imaging ; Brain Neoplasms - drug therapy ; Brain Neoplasms - pathology ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Disease Models, Animal ; Drug Carriers - chemistry ; Drug Carriers - pharmacology ; Drug Delivery Systems ; Drug Screening Assays, Antitumor ; Glioma ; Glioma - diagnostic imaging ; Glioma - drug therapy ; Glioma - pathology ; Graphite - chemistry ; Graphite - pharmacology ; Magnetic Resonance Imaging ; Magnetic targeting ; Magnetite Nanoparticles - chemistry ; Male ; Nano-graphene oxide ; Optical Imaging ; Oxides - chemistry ; Oxides - pharmacology ; Particle Size ; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer - pharmacology ; Rats ; Rats, Wistar ; Superparamagnetic iron oxide ; Tumor Cells, Cultured ; Uridine - analogs & derivatives ; Uridine - chemistry ; Uridine - pharmacology</subject><ispartof>Chemico-biological interactions, 2018-11, Vol.295, p.97-108</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-70ce8e256f2fe1ccede826bae360ebbfd88788466b6aded4b971343c2ebf01b63</citedby><cites>FETCH-LOGICAL-c353t-70ce8e256f2fe1ccede826bae360ebbfd88788466b6aded4b971343c2ebf01b63</cites><orcidid>0000-0003-3213-8824 ; 0000-0002-2847-9223</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cbi.2018.08.027$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30170108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shirvalilou, Sakine</creatorcontrib><creatorcontrib>Khoei, Samideh</creatorcontrib><creatorcontrib>Khoee, Sepideh</creatorcontrib><creatorcontrib>Raoufi, Nida Jamali</creatorcontrib><creatorcontrib>Karimi, Mohammad Reza</creatorcontrib><creatorcontrib>Shakeri-Zadeh, Ali</creatorcontrib><title>Development of a magnetic nano-graphene oxide carrier for improved glioma-targeted drug delivery and imaging: In vitro and in vivo evaluations</title><title>Chemico-biological interactions</title><addtitle>Chem Biol Interact</addtitle><description>To overcome the obstacles inflicted by the BBB in Glioblastoma multiforme (GBM) we investigated the use of Multifunctional nanoparticles that designed with a Nano-graphene oxide (NGO) sheet functionalized with magnetic poly (lactic-co-glycolic acid) (PLGA) and was used for glioma targeting delivery of radiosensitizing 5-iodo-2-deoxyuridine (IUdR). In vitro biocompatibility of nanocomposite has been studied by the MTT assay. In vivo efficacy of magnetic targeting on the amount and selectivity of magnetic nanoparticles accumulation in glioma-bearing rats under an external magnetic field (EMF) density of 0.5 T was easily monitored with MRI. IUdR-loaded magnetic NGO/PLGA with a diameter of 71.8 nm, a zeta potential of −33.07 ± 0.07 mV, and a drug loading content of 3.04 ± 0.46% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 15.98 emu/g. Furthermore, Prussian blue staining showed effective magnetic targeting, leading to remarkably improved tumor inhibitory efficiency of IUdR. The tumor volume of rats after treatment with IUdR/NGO/SPION/PLGA + MF was decreased significantly compared to the rats treated with buffer saline, IUdR and SPION/IUdR/NGO/PLGA. Most importantly, our data demonstrate that IUdR/NGO/SPION/PLGA at the present magnetic field prolongs the median survival time of animals bearing gliomas (38 days, p < 0.01). Nanoparticles also had high thermal sensitivities under the alternating magnetic field. In conclusion, we developed magnetic IUdR/NGO/PLGA, which not only achieved to high accumulation at the targeted tumor site by magnetic targeting but also indicated significantly enhanced therapeutic efficiency and toxicity for glioma both in vitro and in vivo. This innovation increases the possibility of improving clinical efficiency of IUdR as a radiosensitizer, or lowering the total drug dose to decrease systemic toxicity.
Schematic illustration of magnetic drug delivery, verified by staining and use as an MRI contrast agent with IUdR/GO/SPION/PLGA and MF. [Display omitted]
•IUdR-loaded magnetic NGO + MF indicated the strongest anticancer effects in rat gliomas.•Magnetic NGO induces thermosensitising effects in alternative magnetic field.•Magnetic NGO under external magnetic field could overcome the BBB.•Magnetic NGO could enhance the MRI sensitivity.•Magnetic NGO modified with PLGA showed sustained release of IUdR.</description><subject>5-Iodo-2′-deoxyuridine</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Brain Neoplasms - diagnostic imaging</subject><subject>Brain Neoplasms - drug therapy</subject><subject>Brain Neoplasms - pathology</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Disease Models, Animal</subject><subject>Drug Carriers - chemistry</subject><subject>Drug Carriers - pharmacology</subject><subject>Drug Delivery Systems</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Glioma</subject><subject>Glioma - diagnostic imaging</subject><subject>Glioma - drug therapy</subject><subject>Glioma - pathology</subject><subject>Graphite - chemistry</subject><subject>Graphite - pharmacology</subject><subject>Magnetic Resonance Imaging</subject><subject>Magnetic targeting</subject><subject>Magnetite Nanoparticles - chemistry</subject><subject>Male</subject><subject>Nano-graphene oxide</subject><subject>Optical Imaging</subject><subject>Oxides - chemistry</subject><subject>Oxides - pharmacology</subject><subject>Particle Size</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - chemistry</subject><subject>Polylactic Acid-Polyglycolic Acid Copolymer - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Superparamagnetic iron oxide</subject><subject>Tumor Cells, Cultured</subject><subject>Uridine - analogs & derivatives</subject><subject>Uridine - chemistry</subject><subject>Uridine - pharmacology</subject><issn>0009-2797</issn><issn>1872-7786</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2KFDEUhYMoTjv6AG4kSzfV3qR6krSuZNRxYMCNrkN-bpVpqpI2SRXOS_jMpunR5cCFcMJ3D5x7CHnNYMuAiXeHrbNhy4GpLbTh8gnZMCV5J6UST8kGAPYdl3t5QV6UcmgS-A6ek4semAQGakP-fMIVp3ScMVaaBmrobMaINTgaTUzdmM3xJ0ak6XfwSJ3JOWCmQ8o0zMecVvR0nEKaTVdNHrE27fMyUo9TWDHfUxN9Q80Y4vie3ka6hprT-fck1kRxNdNiakixvCTPBjMVfPXwXpIfXz5_v_7a3X27ub3-eNe5_qqvnQSHCvmVGPiAzDn0qLiwBnsBaO3glZJK7YSwwnj0O7uXrN_1jqMdgFnRX5K3Z98W4deCpeo5FIfTZCKmpWgOeyUl73vVUHZGXU6lZBz0Mbc8-V4z0Kca9EG3GvSpBg1tuGw7bx7sFzuj_7_x7-4N-HAGsIVc20V1cQFjCxIyuqp9Co_Y_wXcZpuW</recordid><startdate>20181101</startdate><enddate>20181101</enddate><creator>Shirvalilou, Sakine</creator><creator>Khoei, Samideh</creator><creator>Khoee, Sepideh</creator><creator>Raoufi, Nida Jamali</creator><creator>Karimi, Mohammad Reza</creator><creator>Shakeri-Zadeh, Ali</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3213-8824</orcidid><orcidid>https://orcid.org/0000-0002-2847-9223</orcidid></search><sort><creationdate>20181101</creationdate><title>Development of a magnetic nano-graphene oxide carrier for improved glioma-targeted drug delivery and imaging: In vitro and in vivo evaluations</title><author>Shirvalilou, Sakine ; Khoei, Samideh ; Khoee, Sepideh ; Raoufi, Nida Jamali ; Karimi, Mohammad Reza ; Shakeri-Zadeh, Ali</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-70ce8e256f2fe1ccede826bae360ebbfd88788466b6aded4b971343c2ebf01b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>5-Iodo-2′-deoxyuridine</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Brain Neoplasms - diagnostic imaging</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain Neoplasms - pathology</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Disease Models, Animal</topic><topic>Drug Carriers - chemistry</topic><topic>Drug Carriers - pharmacology</topic><topic>Drug Delivery Systems</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Glioma</topic><topic>Glioma - diagnostic imaging</topic><topic>Glioma - drug therapy</topic><topic>Glioma - pathology</topic><topic>Graphite - chemistry</topic><topic>Graphite - pharmacology</topic><topic>Magnetic Resonance Imaging</topic><topic>Magnetic targeting</topic><topic>Magnetite Nanoparticles - chemistry</topic><topic>Male</topic><topic>Nano-graphene oxide</topic><topic>Optical Imaging</topic><topic>Oxides - chemistry</topic><topic>Oxides - pharmacology</topic><topic>Particle Size</topic><topic>Polylactic Acid-Polyglycolic Acid Copolymer - chemistry</topic><topic>Polylactic Acid-Polyglycolic Acid Copolymer - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Superparamagnetic iron oxide</topic><topic>Tumor Cells, Cultured</topic><topic>Uridine - analogs & derivatives</topic><topic>Uridine - chemistry</topic><topic>Uridine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shirvalilou, Sakine</creatorcontrib><creatorcontrib>Khoei, Samideh</creatorcontrib><creatorcontrib>Khoee, Sepideh</creatorcontrib><creatorcontrib>Raoufi, Nida Jamali</creatorcontrib><creatorcontrib>Karimi, Mohammad Reza</creatorcontrib><creatorcontrib>Shakeri-Zadeh, Ali</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chemico-biological interactions</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shirvalilou, Sakine</au><au>Khoei, Samideh</au><au>Khoee, Sepideh</au><au>Raoufi, Nida Jamali</au><au>Karimi, Mohammad Reza</au><au>Shakeri-Zadeh, Ali</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a magnetic nano-graphene oxide carrier for improved glioma-targeted drug delivery and imaging: In vitro and in vivo evaluations</atitle><jtitle>Chemico-biological interactions</jtitle><addtitle>Chem Biol Interact</addtitle><date>2018-11-01</date><risdate>2018</risdate><volume>295</volume><spage>97</spage><epage>108</epage><pages>97-108</pages><issn>0009-2797</issn><eissn>1872-7786</eissn><abstract>To overcome the obstacles inflicted by the BBB in Glioblastoma multiforme (GBM) we investigated the use of Multifunctional nanoparticles that designed with a Nano-graphene oxide (NGO) sheet functionalized with magnetic poly (lactic-co-glycolic acid) (PLGA) and was used for glioma targeting delivery of radiosensitizing 5-iodo-2-deoxyuridine (IUdR). In vitro biocompatibility of nanocomposite has been studied by the MTT assay. In vivo efficacy of magnetic targeting on the amount and selectivity of magnetic nanoparticles accumulation in glioma-bearing rats under an external magnetic field (EMF) density of 0.5 T was easily monitored with MRI. IUdR-loaded magnetic NGO/PLGA with a diameter of 71.8 nm, a zeta potential of −33.07 ± 0.07 mV, and a drug loading content of 3.04 ± 0.46% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 15.98 emu/g. Furthermore, Prussian blue staining showed effective magnetic targeting, leading to remarkably improved tumor inhibitory efficiency of IUdR. The tumor volume of rats after treatment with IUdR/NGO/SPION/PLGA + MF was decreased significantly compared to the rats treated with buffer saline, IUdR and SPION/IUdR/NGO/PLGA. Most importantly, our data demonstrate that IUdR/NGO/SPION/PLGA at the present magnetic field prolongs the median survival time of animals bearing gliomas (38 days, p < 0.01). Nanoparticles also had high thermal sensitivities under the alternating magnetic field. In conclusion, we developed magnetic IUdR/NGO/PLGA, which not only achieved to high accumulation at the targeted tumor site by magnetic targeting but also indicated significantly enhanced therapeutic efficiency and toxicity for glioma both in vitro and in vivo. This innovation increases the possibility of improving clinical efficiency of IUdR as a radiosensitizer, or lowering the total drug dose to decrease systemic toxicity.
Schematic illustration of magnetic drug delivery, verified by staining and use as an MRI contrast agent with IUdR/GO/SPION/PLGA and MF. [Display omitted]
•IUdR-loaded magnetic NGO + MF indicated the strongest anticancer effects in rat gliomas.•Magnetic NGO induces thermosensitising effects in alternative magnetic field.•Magnetic NGO under external magnetic field could overcome the BBB.•Magnetic NGO could enhance the MRI sensitivity.•Magnetic NGO modified with PLGA showed sustained release of IUdR.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>30170108</pmid><doi>10.1016/j.cbi.2018.08.027</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-3213-8824</orcidid><orcidid>https://orcid.org/0000-0002-2847-9223</orcidid></addata></record> |
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| ispartof | Chemico-biological interactions, 2018-11, Vol.295, p.97-108 |
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| subjects | 5-Iodo-2′-deoxyuridine Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Brain Neoplasms - diagnostic imaging Brain Neoplasms - drug therapy Brain Neoplasms - pathology Cell Proliferation - drug effects Cell Survival - drug effects Disease Models, Animal Drug Carriers - chemistry Drug Carriers - pharmacology Drug Delivery Systems Drug Screening Assays, Antitumor Glioma Glioma - diagnostic imaging Glioma - drug therapy Glioma - pathology Graphite - chemistry Graphite - pharmacology Magnetic Resonance Imaging Magnetic targeting Magnetite Nanoparticles - chemistry Male Nano-graphene oxide Optical Imaging Oxides - chemistry Oxides - pharmacology Particle Size Polylactic Acid-Polyglycolic Acid Copolymer - chemistry Polylactic Acid-Polyglycolic Acid Copolymer - pharmacology Rats Rats, Wistar Superparamagnetic iron oxide Tumor Cells, Cultured Uridine - analogs & derivatives Uridine - chemistry Uridine - pharmacology |
| title | Development of a magnetic nano-graphene oxide carrier for improved glioma-targeted drug delivery and imaging: In vitro and in vivo evaluations |
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