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Responsive Nanomicellar Theranostic Cages for Metastatic Breast Cancer
Precluding the progression of metastasis with early diagnosis of triple-negative breast cancer remains challenging due to lack of targeting specificity with poor diagnostic potential. Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30–45 nm) comprising doxorubicin–superpara...
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| Published in: | Bioconjugate chemistry 2018-02, Vol.29 (2), p.275-286 |
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| Main Authors: | , , , , , , |
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| cited_by | cdi_FETCH-LOGICAL-a439t-76b1d7434a1a9ff5b910f1fd9c459b9b32f908a227b644203c98dff8d5b4a7753 |
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| cites | cdi_FETCH-LOGICAL-a439t-76b1d7434a1a9ff5b910f1fd9c459b9b32f908a227b644203c98dff8d5b4a7753 |
| container_end_page | 286 |
| container_issue | 2 |
| container_start_page | 275 |
| container_title | Bioconjugate chemistry |
| container_volume | 29 |
| creator | Manigandan, Amrutha Handi, Vandhana Sundaramoorthy, Niranjana Sri Dhandapani, Ramya Radhakrishnan, Janani Sethuraman, Swaminathan Subramanian, Anuradha |
| description | Precluding the progression of metastasis with early diagnosis of triple-negative breast cancer remains challenging due to lack of targeting specificity with poor diagnostic potential. Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30–45 nm) comprising doxorubicin–superparamagnetic iron oxide nanoparticles complexes (89.23%) with lower critical micelle concentration (0.1 μg/mL) were developed. Micelles exhibit concentration-based contrast enhancement in MRI (r2 6.27 mM–1 s–1) and hyperthermia rather than thermal-ablation. This theranostics delivers doxorubicin under alternating magnetic field (480 kHz) and at endosomal pH (pH 5.2) while showing stability at pH 7.4. Anti-αvβ3 integrin antibody conjugation onto PEGylated micelles (62.3%) enhances micellar internalization into drug-resistant MDA-MB-231 after 1 h and magnetizes the cells after 6 h over that with nonconjugated micelles. Immigration of MDA-MB-231 and 4T1 cells retards after 24 h, while significant reduction of mitochondrial membrane potential is observed under hyperthermia. Intratumoral administration of nanomicelles in 4T1 orthotopic spontaneous metastasis model demonstrated antitumor and fibrosis mediated caging effect with simultaneous enhancement of MRI-T2 contrast. |
| doi_str_mv | 10.1021/acs.bioconjchem.7b00577 |
| format | article |
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Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30–45 nm) comprising doxorubicin–superparamagnetic iron oxide nanoparticles complexes (89.23%) with lower critical micelle concentration (0.1 μg/mL) were developed. Micelles exhibit concentration-based contrast enhancement in MRI (r2 6.27 mM–1 s–1) and hyperthermia rather than thermal-ablation. This theranostics delivers doxorubicin under alternating magnetic field (480 kHz) and at endosomal pH (pH 5.2) while showing stability at pH 7.4. Anti-αvβ3 integrin antibody conjugation onto PEGylated micelles (62.3%) enhances micellar internalization into drug-resistant MDA-MB-231 after 1 h and magnetizes the cells after 6 h over that with nonconjugated micelles. Immigration of MDA-MB-231 and 4T1 cells retards after 24 h, while significant reduction of mitochondrial membrane potential is observed under hyperthermia. Intratumoral administration of nanomicelles in 4T1 orthotopic spontaneous metastasis model demonstrated antitumor and fibrosis mediated caging effect with simultaneous enhancement of MRI-T2 contrast.</description><identifier>ISSN: 1043-1802</identifier><identifier>EISSN: 1520-4812</identifier><identifier>DOI: 10.1021/acs.bioconjchem.7b00577</identifier><identifier>PMID: 29281265</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Antibiotics, Antineoplastic - administration & dosage ; Antibiotics, Antineoplastic - therapeutic use ; Breast cancer ; Cages ; Cancer ; Cell Line, Tumor ; Cells ; Chitosan ; Chitosan - chemistry ; Conjugation ; Coordination compounds ; Diagnostic systems ; Doxorubicin ; Doxorubicin - administration & dosage ; Doxorubicin - therapeutic use ; Drug Delivery Systems ; Drug resistance ; Female ; Fibrosis ; Humans ; Hyperthermia ; Immigration ; Immunoconjugates - administration & dosage ; Immunoconjugates - therapeutic use ; Internalization ; Iron oxides ; Magnetic fields ; Magnetic resonance imaging ; Magnetic Resonance Imaging - methods ; Magnetite Nanoparticles - chemistry ; Membrane potential ; Metastases ; Mice, Inbred BALB C ; Mice, Nude ; Micelles ; Mitochondria ; Nanoparticles ; pH effects ; Precision medicine ; Theranostic Nanomedicine - methods ; Transmission electron microscopy ; Triple Negative Breast Neoplasms - diagnostic imaging ; Triple Negative Breast Neoplasms - drug therapy ; Vitamin E</subject><ispartof>Bioconjugate chemistry, 2018-02, Vol.29 (2), p.275-286</ispartof><rights>Copyright © 2017 American Chemical Society</rights><rights>Copyright American Chemical Society Feb 21, 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a439t-76b1d7434a1a9ff5b910f1fd9c459b9b32f908a227b644203c98dff8d5b4a7753</citedby><cites>FETCH-LOGICAL-a439t-76b1d7434a1a9ff5b910f1fd9c459b9b32f908a227b644203c98dff8d5b4a7753</cites><orcidid>0000-0001-7333-0244</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27936,27937</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29281265$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Manigandan, Amrutha</creatorcontrib><creatorcontrib>Handi, Vandhana</creatorcontrib><creatorcontrib>Sundaramoorthy, Niranjana Sri</creatorcontrib><creatorcontrib>Dhandapani, Ramya</creatorcontrib><creatorcontrib>Radhakrishnan, Janani</creatorcontrib><creatorcontrib>Sethuraman, Swaminathan</creatorcontrib><creatorcontrib>Subramanian, Anuradha</creatorcontrib><title>Responsive Nanomicellar Theranostic Cages for Metastatic Breast Cancer</title><title>Bioconjugate chemistry</title><addtitle>Bioconjugate Chem</addtitle><description>Precluding the progression of metastasis with early diagnosis of triple-negative breast cancer remains challenging due to lack of targeting specificity with poor diagnostic potential. Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30–45 nm) comprising doxorubicin–superparamagnetic iron oxide nanoparticles complexes (89.23%) with lower critical micelle concentration (0.1 μg/mL) were developed. Micelles exhibit concentration-based contrast enhancement in MRI (r2 6.27 mM–1 s–1) and hyperthermia rather than thermal-ablation. This theranostics delivers doxorubicin under alternating magnetic field (480 kHz) and at endosomal pH (pH 5.2) while showing stability at pH 7.4. Anti-αvβ3 integrin antibody conjugation onto PEGylated micelles (62.3%) enhances micellar internalization into drug-resistant MDA-MB-231 after 1 h and magnetizes the cells after 6 h over that with nonconjugated micelles. Immigration of MDA-MB-231 and 4T1 cells retards after 24 h, while significant reduction of mitochondrial membrane potential is observed under hyperthermia. Intratumoral administration of nanomicelles in 4T1 orthotopic spontaneous metastasis model demonstrated antitumor and fibrosis mediated caging effect with simultaneous enhancement of MRI-T2 contrast.</description><subject>Animals</subject><subject>Antibiotics, Antineoplastic - administration & dosage</subject><subject>Antibiotics, Antineoplastic - therapeutic use</subject><subject>Breast cancer</subject><subject>Cages</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cells</subject><subject>Chitosan</subject><subject>Chitosan - chemistry</subject><subject>Conjugation</subject><subject>Coordination compounds</subject><subject>Diagnostic systems</subject><subject>Doxorubicin</subject><subject>Doxorubicin - administration & dosage</subject><subject>Doxorubicin - therapeutic use</subject><subject>Drug Delivery Systems</subject><subject>Drug resistance</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Humans</subject><subject>Hyperthermia</subject><subject>Immigration</subject><subject>Immunoconjugates - administration & dosage</subject><subject>Immunoconjugates - therapeutic use</subject><subject>Internalization</subject><subject>Iron oxides</subject><subject>Magnetic fields</subject><subject>Magnetic resonance imaging</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Magnetite Nanoparticles - chemistry</subject><subject>Membrane potential</subject><subject>Metastases</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Micelles</subject><subject>Mitochondria</subject><subject>Nanoparticles</subject><subject>pH effects</subject><subject>Precision medicine</subject><subject>Theranostic Nanomedicine - methods</subject><subject>Transmission electron microscopy</subject><subject>Triple Negative Breast Neoplasms - diagnostic imaging</subject><subject>Triple Negative Breast Neoplasms - drug therapy</subject><subject>Vitamin E</subject><issn>1043-1802</issn><issn>1520-4812</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNqFkMtOAyEUhonR2Fp9BZ3EjZupXIdhqY1VEy-JqWsCDNhpOkOFGRPfXmprY9y44gDf-c_JB8AZgmMEMbpUJo517Y1vF2ZumzHXEDLO98AQMQxzWiK8n2pISY5KiAfgKMYFhFCgEh-CARY4EQUbgumLjSvfxvrDZk-q9U1t7HKpQjab25DusatNNlFvNmbOh-zRdip2av14HWwq019rbDgGB04toz3ZniPwOr2ZTe7yh-fb-8nVQ64oEV3OC40qTglVSAnnmBYIOuQqYSgTWmiCnYClwpjrglIMiRFl5VxZMU0V54yMwMUmdxX8e29jJ5s6fm_cWt9HiUSJOIecoISe_0EXvg9t2k5iiBjHTJAiUXxDmeBjDNbJVagbFT4lgnKtWibV8pdquVWdOk-3-b1ubLXr-3GbALIB1gm72f_FfgE-Io9i</recordid><startdate>20180221</startdate><enddate>20180221</enddate><creator>Manigandan, Amrutha</creator><creator>Handi, Vandhana</creator><creator>Sundaramoorthy, Niranjana Sri</creator><creator>Dhandapani, Ramya</creator><creator>Radhakrishnan, Janani</creator><creator>Sethuraman, Swaminathan</creator><creator>Subramanian, Anuradha</creator><general>American Chemical Society</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7333-0244</orcidid></search><sort><creationdate>20180221</creationdate><title>Responsive Nanomicellar Theranostic Cages for Metastatic Breast Cancer</title><author>Manigandan, Amrutha ; Handi, Vandhana ; Sundaramoorthy, Niranjana Sri ; Dhandapani, Ramya ; Radhakrishnan, Janani ; Sethuraman, Swaminathan ; Subramanian, Anuradha</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a439t-76b1d7434a1a9ff5b910f1fd9c459b9b32f908a227b644203c98dff8d5b4a7753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antibiotics, Antineoplastic - administration & dosage</topic><topic>Antibiotics, Antineoplastic - therapeutic use</topic><topic>Breast cancer</topic><topic>Cages</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cells</topic><topic>Chitosan</topic><topic>Chitosan - chemistry</topic><topic>Conjugation</topic><topic>Coordination compounds</topic><topic>Diagnostic systems</topic><topic>Doxorubicin</topic><topic>Doxorubicin - administration & dosage</topic><topic>Doxorubicin - therapeutic use</topic><topic>Drug Delivery Systems</topic><topic>Drug resistance</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Humans</topic><topic>Hyperthermia</topic><topic>Immigration</topic><topic>Immunoconjugates - administration & dosage</topic><topic>Immunoconjugates - therapeutic use</topic><topic>Internalization</topic><topic>Iron oxides</topic><topic>Magnetic fields</topic><topic>Magnetic resonance imaging</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Magnetite Nanoparticles - chemistry</topic><topic>Membrane potential</topic><topic>Metastases</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Micelles</topic><topic>Mitochondria</topic><topic>Nanoparticles</topic><topic>pH effects</topic><topic>Precision medicine</topic><topic>Theranostic Nanomedicine - methods</topic><topic>Transmission electron microscopy</topic><topic>Triple Negative Breast Neoplasms - diagnostic imaging</topic><topic>Triple Negative Breast Neoplasms - drug therapy</topic><topic>Vitamin E</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Manigandan, Amrutha</creatorcontrib><creatorcontrib>Handi, Vandhana</creatorcontrib><creatorcontrib>Sundaramoorthy, Niranjana Sri</creatorcontrib><creatorcontrib>Dhandapani, Ramya</creatorcontrib><creatorcontrib>Radhakrishnan, Janani</creatorcontrib><creatorcontrib>Sethuraman, Swaminathan</creatorcontrib><creatorcontrib>Subramanian, Anuradha</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bioconjugate chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Manigandan, Amrutha</au><au>Handi, Vandhana</au><au>Sundaramoorthy, Niranjana Sri</au><au>Dhandapani, Ramya</au><au>Radhakrishnan, Janani</au><au>Sethuraman, Swaminathan</au><au>Subramanian, Anuradha</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Responsive Nanomicellar Theranostic Cages for Metastatic Breast Cancer</atitle><jtitle>Bioconjugate chemistry</jtitle><addtitle>Bioconjugate Chem</addtitle><date>2018-02-21</date><risdate>2018</risdate><volume>29</volume><issue>2</issue><spage>275</spage><epage>286</epage><pages>275-286</pages><issn>1043-1802</issn><eissn>1520-4812</eissn><abstract>Precluding the progression of metastasis with early diagnosis of triple-negative breast cancer remains challenging due to lack of targeting specificity with poor diagnostic potential. Herein, an amphipathic chitosan-based targeted nanomicellar theranostics (30–45 nm) comprising doxorubicin–superparamagnetic iron oxide nanoparticles complexes (89.23%) with lower critical micelle concentration (0.1 μg/mL) were developed. Micelles exhibit concentration-based contrast enhancement in MRI (r2 6.27 mM–1 s–1) and hyperthermia rather than thermal-ablation. This theranostics delivers doxorubicin under alternating magnetic field (480 kHz) and at endosomal pH (pH 5.2) while showing stability at pH 7.4. Anti-αvβ3 integrin antibody conjugation onto PEGylated micelles (62.3%) enhances micellar internalization into drug-resistant MDA-MB-231 after 1 h and magnetizes the cells after 6 h over that with nonconjugated micelles. Immigration of MDA-MB-231 and 4T1 cells retards after 24 h, while significant reduction of mitochondrial membrane potential is observed under hyperthermia. Intratumoral administration of nanomicelles in 4T1 orthotopic spontaneous metastasis model demonstrated antitumor and fibrosis mediated caging effect with simultaneous enhancement of MRI-T2 contrast.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>29281265</pmid><doi>10.1021/acs.bioconjchem.7b00577</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-7333-0244</orcidid></addata></record> |
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| ispartof | Bioconjugate chemistry, 2018-02, Vol.29 (2), p.275-286 |
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| language | eng |
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| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | Animals Antibiotics, Antineoplastic - administration & dosage Antibiotics, Antineoplastic - therapeutic use Breast cancer Cages Cancer Cell Line, Tumor Cells Chitosan Chitosan - chemistry Conjugation Coordination compounds Diagnostic systems Doxorubicin Doxorubicin - administration & dosage Doxorubicin - therapeutic use Drug Delivery Systems Drug resistance Female Fibrosis Humans Hyperthermia Immigration Immunoconjugates - administration & dosage Immunoconjugates - therapeutic use Internalization Iron oxides Magnetic fields Magnetic resonance imaging Magnetic Resonance Imaging - methods Magnetite Nanoparticles - chemistry Membrane potential Metastases Mice, Inbred BALB C Mice, Nude Micelles Mitochondria Nanoparticles pH effects Precision medicine Theranostic Nanomedicine - methods Transmission electron microscopy Triple Negative Breast Neoplasms - diagnostic imaging Triple Negative Breast Neoplasms - drug therapy Vitamin E |
| title | Responsive Nanomicellar Theranostic Cages for Metastatic Breast Cancer |
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