Magnetically Guided Self-Assembled Protein Micelles for Enhanced Delivery of Dasatinib to Human Triple-Negative Breast Cancer Cells
Magnetic nanocarriers are useful in targeted cancer therapy. Dasatinib (DAS)-loaded magnetic micelles were prepared for magnetically guided drug delivery. The magnetic nanoplatform is composed of hydrophobic oleic acid–coated magnetite (Fe3O4) core along with DAS encapsulated in amphiphilic zein-lac...
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Veröffentlicht in: | Journal of pharmaceutical sciences 2019-05, Vol.108 (5), p.1713-1725 |
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creator | Sabra, Sally A. Sheweita, Salah A. Haroun, Medhat Ragab, Doaa Eldemellawy, Maha A. Xia, Ying Goodale, David Allan, Alison L. Elzoghby, Ahmed O. Rohani, Sohrab |
description | Magnetic nanocarriers are useful in targeted cancer therapy. Dasatinib (DAS)-loaded magnetic micelles were prepared for magnetically guided drug delivery. The magnetic nanoplatform is composed of hydrophobic oleic acid–coated magnetite (Fe3O4) core along with DAS encapsulated in amphiphilic zein-lactoferrin self-assembled polymeric micelles. Transmission electron microscope analysis manifested formation of these magnetic micelles with a mean diameter of about 100 nm. In addition, drug-loaded magnetic micelles displayed a saturation magnetization of about 10.01 emu.g−1 with a superparamagnetic property. They also showed good in vitro serum stability and hemocompatibility accompanied with a sustained release of DAS in acidic pH. More importantly, they exhibited 1.35-fold increase in their in vitro cytotoxicity against triple-negative human breast cancer cell line (MDA-MB-231) using an external magnetic field compared to drug-loaded magnetic micelles in the absence of a magnetic field. Enhanced inhibition of p-c-Src protein expression level and in vitro cellular migration under the effect of magnetic field was noted owing to the dual-targeting strategy offered by the presence of a magnetic sensitive core, as well as the active targeting property of lactoferrin corona. Taken all together, these results suggest that DAS-loaded magnetic micelles possess a great potential for targeted therapy of breast cancer. |
doi_str_mv | 10.1016/j.xphs.2018.11.044 |
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Dasatinib (DAS)-loaded magnetic micelles were prepared for magnetically guided drug delivery. The magnetic nanoplatform is composed of hydrophobic oleic acid–coated magnetite (Fe3O4) core along with DAS encapsulated in amphiphilic zein-lactoferrin self-assembled polymeric micelles. Transmission electron microscope analysis manifested formation of these magnetic micelles with a mean diameter of about 100 nm. In addition, drug-loaded magnetic micelles displayed a saturation magnetization of about 10.01 emu.g−1 with a superparamagnetic property. They also showed good in vitro serum stability and hemocompatibility accompanied with a sustained release of DAS in acidic pH. More importantly, they exhibited 1.35-fold increase in their in vitro cytotoxicity against triple-negative human breast cancer cell line (MDA-MB-231) using an external magnetic field compared to drug-loaded magnetic micelles in the absence of a magnetic field. Enhanced inhibition of p-c-Src protein expression level and in vitro cellular migration under the effect of magnetic field was noted owing to the dual-targeting strategy offered by the presence of a magnetic sensitive core, as well as the active targeting property of lactoferrin corona. Taken all together, these results suggest that DAS-loaded magnetic micelles possess a great potential for targeted therapy of breast cancer.</description><identifier>ISSN: 0022-3549</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1016/j.xphs.2018.11.044</identifier><identifier>PMID: 30528944</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>cancer chemotherapy ; controlled delivery ; controlled release ; drug targeting ; micelle(s) ; nanotechnology ; polymeric drug carrier(s)</subject><ispartof>Journal of pharmaceutical sciences, 2019-05, Vol.108 (5), p.1713-1725</ispartof><rights>2019</rights><rights>Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-3d149d20d803066db46e2e1e0be01f1cbcb566274d6cba4dc19fa2e5130f9c163</citedby><cites>FETCH-LOGICAL-c356t-3d149d20d803066db46e2e1e0be01f1cbcb566274d6cba4dc19fa2e5130f9c163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27933,27934</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30528944$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sabra, Sally A.</creatorcontrib><creatorcontrib>Sheweita, Salah A.</creatorcontrib><creatorcontrib>Haroun, Medhat</creatorcontrib><creatorcontrib>Ragab, Doaa</creatorcontrib><creatorcontrib>Eldemellawy, Maha A.</creatorcontrib><creatorcontrib>Xia, Ying</creatorcontrib><creatorcontrib>Goodale, David</creatorcontrib><creatorcontrib>Allan, Alison L.</creatorcontrib><creatorcontrib>Elzoghby, Ahmed O.</creatorcontrib><creatorcontrib>Rohani, Sohrab</creatorcontrib><title>Magnetically Guided Self-Assembled Protein Micelles for Enhanced Delivery of Dasatinib to Human Triple-Negative Breast Cancer Cells</title><title>Journal of pharmaceutical sciences</title><addtitle>J Pharm Sci</addtitle><description>Magnetic nanocarriers are useful in targeted cancer therapy. Dasatinib (DAS)-loaded magnetic micelles were prepared for magnetically guided drug delivery. The magnetic nanoplatform is composed of hydrophobic oleic acid–coated magnetite (Fe3O4) core along with DAS encapsulated in amphiphilic zein-lactoferrin self-assembled polymeric micelles. Transmission electron microscope analysis manifested formation of these magnetic micelles with a mean diameter of about 100 nm. In addition, drug-loaded magnetic micelles displayed a saturation magnetization of about 10.01 emu.g−1 with a superparamagnetic property. They also showed good in vitro serum stability and hemocompatibility accompanied with a sustained release of DAS in acidic pH. More importantly, they exhibited 1.35-fold increase in their in vitro cytotoxicity against triple-negative human breast cancer cell line (MDA-MB-231) using an external magnetic field compared to drug-loaded magnetic micelles in the absence of a magnetic field. Enhanced inhibition of p-c-Src protein expression level and in vitro cellular migration under the effect of magnetic field was noted owing to the dual-targeting strategy offered by the presence of a magnetic sensitive core, as well as the active targeting property of lactoferrin corona. Taken all together, these results suggest that DAS-loaded magnetic micelles possess a great potential for targeted therapy of breast cancer.</description><subject>cancer chemotherapy</subject><subject>controlled delivery</subject><subject>controlled release</subject><subject>drug targeting</subject><subject>micelle(s)</subject><subject>nanotechnology</subject><subject>polymeric drug carrier(s)</subject><issn>0022-3549</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kE1v1DAQhi0EokvhD3BAPnJJOuPY3o3EpWxLW6mllShny7EnrVf5WOxk1T3zx0m0pceeRqP3Q3ofxj4j5AioTzb50_Yx5QJwlSPmIOUbtkAlINOAy7dsASBEVihZHrEPKW0AQINS79lRAUqsSikX7O-NfehoCM42zZ5fjMGT57-oqbPTlKitmum9i_1AoeM3wVHTUOJ1H_l592g7N6ln1IQdxT3va35mkx1CFyo-9PxybG3H72PYNpT9pIdJ2RH_Hsmmga_ncOTrqTB9ZO9q2yT69HyP2e8f5_fry-z69uJqfXqduULpISs8ytIL8CsoQGtfSU2CkKAiwBpd5SqltVhKr11lpXdY1laQwgLq0qEujtnXQ-829n9GSoNpQ5on2Y76MRmBSqHC5VJNVnGwutinFKk22xhaG_cGwczwzcbM8M0M3yCaCf4U-vLcP1Yt-ZfIf9qT4dvBQNPKXaBokgs0UwyR3GB8H17r_wc5EpcW</recordid><startdate>201905</startdate><enddate>201905</enddate><creator>Sabra, Sally A.</creator><creator>Sheweita, Salah A.</creator><creator>Haroun, Medhat</creator><creator>Ragab, Doaa</creator><creator>Eldemellawy, Maha A.</creator><creator>Xia, Ying</creator><creator>Goodale, David</creator><creator>Allan, Alison L.</creator><creator>Elzoghby, Ahmed O.</creator><creator>Rohani, Sohrab</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201905</creationdate><title>Magnetically Guided Self-Assembled Protein Micelles for Enhanced Delivery of Dasatinib to Human Triple-Negative Breast Cancer Cells</title><author>Sabra, Sally A. ; Sheweita, Salah A. ; Haroun, Medhat ; Ragab, Doaa ; Eldemellawy, Maha A. ; Xia, Ying ; Goodale, David ; Allan, Alison L. ; Elzoghby, Ahmed O. ; Rohani, Sohrab</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-3d149d20d803066db46e2e1e0be01f1cbcb566274d6cba4dc19fa2e5130f9c163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>cancer chemotherapy</topic><topic>controlled delivery</topic><topic>controlled release</topic><topic>drug targeting</topic><topic>micelle(s)</topic><topic>nanotechnology</topic><topic>polymeric drug carrier(s)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sabra, Sally A.</creatorcontrib><creatorcontrib>Sheweita, Salah A.</creatorcontrib><creatorcontrib>Haroun, Medhat</creatorcontrib><creatorcontrib>Ragab, Doaa</creatorcontrib><creatorcontrib>Eldemellawy, Maha A.</creatorcontrib><creatorcontrib>Xia, Ying</creatorcontrib><creatorcontrib>Goodale, David</creatorcontrib><creatorcontrib>Allan, Alison L.</creatorcontrib><creatorcontrib>Elzoghby, Ahmed O.</creatorcontrib><creatorcontrib>Rohani, Sohrab</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sabra, Sally A.</au><au>Sheweita, Salah A.</au><au>Haroun, Medhat</au><au>Ragab, Doaa</au><au>Eldemellawy, Maha A.</au><au>Xia, Ying</au><au>Goodale, David</au><au>Allan, Alison L.</au><au>Elzoghby, Ahmed O.</au><au>Rohani, Sohrab</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Magnetically Guided Self-Assembled Protein Micelles for Enhanced Delivery of Dasatinib to Human Triple-Negative Breast Cancer Cells</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J Pharm Sci</addtitle><date>2019-05</date><risdate>2019</risdate><volume>108</volume><issue>5</issue><spage>1713</spage><epage>1725</epage><pages>1713-1725</pages><issn>0022-3549</issn><eissn>1520-6017</eissn><abstract>Magnetic nanocarriers are useful in targeted cancer therapy. Dasatinib (DAS)-loaded magnetic micelles were prepared for magnetically guided drug delivery. The magnetic nanoplatform is composed of hydrophobic oleic acid–coated magnetite (Fe3O4) core along with DAS encapsulated in amphiphilic zein-lactoferrin self-assembled polymeric micelles. Transmission electron microscope analysis manifested formation of these magnetic micelles with a mean diameter of about 100 nm. In addition, drug-loaded magnetic micelles displayed a saturation magnetization of about 10.01 emu.g−1 with a superparamagnetic property. They also showed good in vitro serum stability and hemocompatibility accompanied with a sustained release of DAS in acidic pH. More importantly, they exhibited 1.35-fold increase in their in vitro cytotoxicity against triple-negative human breast cancer cell line (MDA-MB-231) using an external magnetic field compared to drug-loaded magnetic micelles in the absence of a magnetic field. Enhanced inhibition of p-c-Src protein expression level and in vitro cellular migration under the effect of magnetic field was noted owing to the dual-targeting strategy offered by the presence of a magnetic sensitive core, as well as the active targeting property of lactoferrin corona. Taken all together, these results suggest that DAS-loaded magnetic micelles possess a great potential for targeted therapy of breast cancer.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>30528944</pmid><doi>10.1016/j.xphs.2018.11.044</doi><tpages>13</tpages></addata></record> |
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subjects | cancer chemotherapy controlled delivery controlled release drug targeting micelle(s) nanotechnology polymeric drug carrier(s) |
title | Magnetically Guided Self-Assembled Protein Micelles for Enhanced Delivery of Dasatinib to Human Triple-Negative Breast Cancer Cells |
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