Nose-to-Brain Delivery of Cancer-Targeting Paclitaxel-Loaded Nanoparticles Potentiates Antitumor Effects in Malignant Glioblastoma
Glioblastoma multiforme (GBM) is an aggressive tumor with no curative treatment. The tumor recurrence after resection often requires chemotherapy or radiation to delay the infiltration of tumor remnants. Intracerebral chemotherapies are preferentially being used to prevent tumor regrowth, but treatm...
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Veröffentlicht in: | Molecular pharmaceutics 2020-04, Vol.17 (4), p.1193-1204 |
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creator | Ullah, Irfan Chung, Kunho Bae, Sumin Li, Yan Kim, Chunggu Choi, Boyoung Nam, Hye Yeong Kim, Sun Hwa Yun, Chae-Ok Lee, Kuen Yong Kumar, Priti Lee, Sang-Kyung |
description | Glioblastoma multiforme (GBM) is an aggressive tumor with no curative treatment. The tumor recurrence after resection often requires chemotherapy or radiation to delay the infiltration of tumor remnants. Intracerebral chemotherapies are preferentially being used to prevent tumor regrowth, but treatments remain unsuccessful because of the poor drug distribution in the brain. In this study, we investigated the therapeutic efficacy of cancer-targeting arginyl-glycyl-aspartic tripeptide (RGD) conjugated paclitaxel (PTX)-loaded nanoparticles (NPs) against GBM by nose-to-brain delivery. Our results demonstrated that RGD-modified PTX-loaded NPs showed cancer-specific delivery and enhanced anticancer effects in vivo. The intranasal (IN) inoculation of RGD-PTX-loaded NPs effectively controls the tumor burden (75 ± 12% reduction) by inducing apoptosis and/or inhibiting cancer cell proliferation without affecting the G0 stage of normal brain cells. Our data provide therapeutic evidence supporting the use of intranasally delivered cancer-targeted PTX-loaded NPs for GBM therapy. |
doi_str_mv | 10.1021/acs.molpharmaceut.9b01215 |
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The tumor recurrence after resection often requires chemotherapy or radiation to delay the infiltration of tumor remnants. Intracerebral chemotherapies are preferentially being used to prevent tumor regrowth, but treatments remain unsuccessful because of the poor drug distribution in the brain. In this study, we investigated the therapeutic efficacy of cancer-targeting arginyl-glycyl-aspartic tripeptide (RGD) conjugated paclitaxel (PTX)-loaded nanoparticles (NPs) against GBM by nose-to-brain delivery. Our results demonstrated that RGD-modified PTX-loaded NPs showed cancer-specific delivery and enhanced anticancer effects in vivo. The intranasal (IN) inoculation of RGD-PTX-loaded NPs effectively controls the tumor burden (75 ± 12% reduction) by inducing apoptosis and/or inhibiting cancer cell proliferation without affecting the G0 stage of normal brain cells. Our data provide therapeutic evidence supporting the use of intranasally delivered cancer-targeted PTX-loaded NPs for GBM therapy.</description><identifier>ISSN: 1543-8384</identifier><identifier>EISSN: 1543-8392</identifier><identifier>DOI: 10.1021/acs.molpharmaceut.9b01215</identifier><identifier>PMID: 31944768</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><ispartof>Molecular pharmaceutics, 2020-04, Vol.17 (4), p.1193-1204</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a363t-11295351d10eae0525b5b314b12f207bf3e31c21c97531755cae9818c0c4c0193</citedby><cites>FETCH-LOGICAL-a363t-11295351d10eae0525b5b314b12f207bf3e31c21c97531755cae9818c0c4c0193</cites><orcidid>0000-0002-5759-5952 ; 0000-0002-1680-7218</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.9b01215$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b01215$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31944768$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ullah, Irfan</creatorcontrib><creatorcontrib>Chung, Kunho</creatorcontrib><creatorcontrib>Bae, Sumin</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Kim, Chunggu</creatorcontrib><creatorcontrib>Choi, Boyoung</creatorcontrib><creatorcontrib>Nam, Hye Yeong</creatorcontrib><creatorcontrib>Kim, Sun Hwa</creatorcontrib><creatorcontrib>Yun, Chae-Ok</creatorcontrib><creatorcontrib>Lee, Kuen Yong</creatorcontrib><creatorcontrib>Kumar, Priti</creatorcontrib><creatorcontrib>Lee, Sang-Kyung</creatorcontrib><title>Nose-to-Brain Delivery of Cancer-Targeting Paclitaxel-Loaded Nanoparticles Potentiates Antitumor Effects in Malignant Glioblastoma</title><title>Molecular pharmaceutics</title><addtitle>Mol. Pharmaceutics</addtitle><description>Glioblastoma multiforme (GBM) is an aggressive tumor with no curative treatment. The tumor recurrence after resection often requires chemotherapy or radiation to delay the infiltration of tumor remnants. Intracerebral chemotherapies are preferentially being used to prevent tumor regrowth, but treatments remain unsuccessful because of the poor drug distribution in the brain. In this study, we investigated the therapeutic efficacy of cancer-targeting arginyl-glycyl-aspartic tripeptide (RGD) conjugated paclitaxel (PTX)-loaded nanoparticles (NPs) against GBM by nose-to-brain delivery. Our results demonstrated that RGD-modified PTX-loaded NPs showed cancer-specific delivery and enhanced anticancer effects in vivo. The intranasal (IN) inoculation of RGD-PTX-loaded NPs effectively controls the tumor burden (75 ± 12% reduction) by inducing apoptosis and/or inhibiting cancer cell proliferation without affecting the G0 stage of normal brain cells. 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Pharmaceutics</addtitle><date>2020-04-06</date><risdate>2020</risdate><volume>17</volume><issue>4</issue><spage>1193</spage><epage>1204</epage><pages>1193-1204</pages><issn>1543-8384</issn><eissn>1543-8392</eissn><abstract>Glioblastoma multiforme (GBM) is an aggressive tumor with no curative treatment. The tumor recurrence after resection often requires chemotherapy or radiation to delay the infiltration of tumor remnants. Intracerebral chemotherapies are preferentially being used to prevent tumor regrowth, but treatments remain unsuccessful because of the poor drug distribution in the brain. In this study, we investigated the therapeutic efficacy of cancer-targeting arginyl-glycyl-aspartic tripeptide (RGD) conjugated paclitaxel (PTX)-loaded nanoparticles (NPs) against GBM by nose-to-brain delivery. Our results demonstrated that RGD-modified PTX-loaded NPs showed cancer-specific delivery and enhanced anticancer effects in vivo. 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title | Nose-to-Brain Delivery of Cancer-Targeting Paclitaxel-Loaded Nanoparticles Potentiates Antitumor Effects in Malignant Glioblastoma |
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