Publication
Radiolabeled block copolymer micelles for image-guided drug delivery
| Summary: | We aimed at exploring block copolymer micelles (BCMs) for the simultaneous delivery of radiation/chemotherapy to cancer cells. To achieve that goal, we have prepared and characterized a novel type of docetaxel (DTX) loaded and non-loaded BCMs. The micelles were decorated with pyrazolyl-diamine chelating units to stabilize the matched pair 99mTc/Re for image-guided delivery of therapeutic drugs. The in vitro studies have shown that DTX release is pH-dependent increasing at lower pH values. Anti-proliferative studies in different cancer cell lines showed that DTX-loaded BCMs present relevant anti-proliferative activity. In comparison to free DTX, the loaded-micelles exhibited higher anti-proliferative activity for the same DTX concentration, which mean that a similar therapeutic outcome may be achieved with reduced side effects. The pyrazolyl-diamine-functionalized micelles were labeled with fac-[99mTc(CO)3(H2O)3]+ in high radiochemical yield and purity. The radiolabeled micelles are stable in phosphate buffer and in cell culture media. Cellular uptake studies in different cancer cell lines indicate a cell type and time-dependent uptake, in agreement with the anti-proliferative activity. Early biodistribution studies in healthy BALB/c mice has shown prolonged circulation lifetime in the bloodstream and relevant in vivo stability, important features when considering an effective DTX delivery system and image-guided delivery agent for cancer theranostics. |
|---|---|
| Main Authors: | Ribeiro, Elisabete |
| Other Authors: | Alho, Irina; Marques, Fernanda; Gano, Lurdes; Correia, Isabel; Correia, João D. G.; Casimiro, Sandra; Costa, Luis; Santos, Isabel Cordeiro; Fernandes, Célia |
| Subject: | (99m)Tc Block copolymer micelle Drug delivery system PEG-b-PCL Radiolabeled micelles |
| Year: | 2016 |
| Country: | Portugal |
| Document type: | article |
| Access type: | restricted access |
| Associated institution: | Universidade de Lisboa |
| Language: | English |
| Origin: | Repositório da Universidade de Lisboa |
| _version_ | 1868467573522169856 |
|---|---|
| author | Ribeiro, Elisabete |
| author2 | Alho, Irina Marques, Fernanda Gano, Lurdes Correia, Isabel Correia, João D. G. Casimiro, Sandra Costa, Luis Santos, Isabel Cordeiro Fernandes, Célia |
| author2_role | author author author author author author author author author |
| author_facet | Ribeiro, Elisabete Alho, Irina Marques, Fernanda Gano, Lurdes Correia, Isabel Correia, João D. G. Casimiro, Sandra Costa, Luis Santos, Isabel Cordeiro Fernandes, Célia |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Ribeiro, Elisabete\",\"Person.identifier.orcid\":\"0000-0001-8103-4744\"},{\"Person.name\":\"Alho, Irina\",\"Person.identifier.orcid\":\"0000-0002-3190-7479\"},{\"Person.name\":\"Marques, Fernanda\",\"Person.identifier.orcid\":\"0000-0001-8440-5299\"},{\"Person.name\":\"Gano, Lurdes\",\"Person.identifier.orcid\":\"0000-0001-7186-2060\"},{\"Person.name\":\"Correia, Isabel\",\"Person.identifier.orcid\":\"0000-0001-7096-4284\"},{\"Person.name\":\"Correia, João D. G.\",\"Person.identifier.orcid\":\"0000-0002-7847-4906\"},{\"Person.name\":\"Casimiro, Sandra\",\"Person.identifier.orcid\":\"0000-0002-6917-4477\"},{\"Person.name\":\"Costa, Luis\",\"Person.identifier.orcid\":\"0000-0002-4782-7318\"},{\"Person.name\":\"Santos, Isabel Cordeiro\",\"Person.identifier.orcid\":\"0000-0001-8350-480X\"},{\"Person.name\":\"Fernandes, Célia\",\"Person.identifier.orcid\":\"0000-0002-2119-8293\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Ribeiro, Elisabete Alho, Irina Marques, Fernanda Gano, Lurdes Correia, Isabel Correia, João D. G. Casimiro, Sandra Costa, Luis Santos, Isabel Cordeiro Fernandes, Célia |
| datacite.date.Accepted.fl_str_mv | 2016-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2022-02-21T17:44:24Z |
| datacite.date.embargoed.fl_str_mv | 2022-02-21T17:44:24Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.subjects.subject.fl_str_mv | (99m)Tc Block copolymer micelle Drug delivery system PEG-b-PCL Radiolabeled micelles |
| datacite.titles.title.fl_str_mv | Radiolabeled block copolymer micelles for image-guided drug delivery |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Ribeiro, Elisabete Alho, Irina Marques, Fernanda Gano, Lurdes Correia, Isabel Correia, João D. G. Casimiro, Sandra Costa, Luis Santos, Isabel Cordeiro Fernandes, Célia |
| dc.date.Accepted.fl_str_mv | 2016-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2022-02-21T17:44:24Z |
| dc.date.embargoed.fl_str_mv | 2022-02-21T17:44:24Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/51440 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| dc.subject.none.fl_str_mv | (99m)Tc Block copolymer micelle Drug delivery system PEG-b-PCL Radiolabeled micelles |
| dc.title.fl_str_mv | Radiolabeled block copolymer micelles for image-guided drug delivery |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | We aimed at exploring block copolymer micelles (BCMs) for the simultaneous delivery of radiation/chemotherapy to cancer cells. To achieve that goal, we have prepared and characterized a novel type of docetaxel (DTX) loaded and non-loaded BCMs. The micelles were decorated with pyrazolyl-diamine chelating units to stabilize the matched pair 99mTc/Re for image-guided delivery of therapeutic drugs. The in vitro studies have shown that DTX release is pH-dependent increasing at lower pH values. Anti-proliferative studies in different cancer cell lines showed that DTX-loaded BCMs present relevant anti-proliferative activity. In comparison to free DTX, the loaded-micelles exhibited higher anti-proliferative activity for the same DTX concentration, which mean that a similar therapeutic outcome may be achieved with reduced side effects. The pyrazolyl-diamine-functionalized micelles were labeled with fac-[99mTc(CO)3(H2O)3]+ in high radiochemical yield and purity. The radiolabeled micelles are stable in phosphate buffer and in cell culture media. Cellular uptake studies in different cancer cell lines indicate a cell type and time-dependent uptake, in agreement with the anti-proliferative activity. Early biodistribution studies in healthy BALB/c mice has shown prolonged circulation lifetime in the bloodstream and relevant in vivo stability, important features when considering an effective DTX delivery system and image-guided delivery agent for cancer theranostics. |
| dirty | 0 |
| eu_rights_str_mv | restrictedAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/188bbb0f-b943-4ad8-8dc1-430ebb6fd1a7/download |
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| identifier.url.fl_str_mv | http://hdl.handle.net/10451/51440 |
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| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/51440 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Ribeiro, Elisabete Ribeiro, Elisabete http://orcid.org/0000-0001-8103-4744 0000-0001-8103-4744 Alho, Irina Alho, Irina https://www.ciencia-id.pt/651D-2E22-AB73 651D-2E22-AB73 http://orcid.org/0000-0002-3190-7479 0000-0002-3190-7479 Marques, Fernanda Marques, Fernanda https://www.ciencia-id.pt/1C11-A0C7-418A 1C11-A0C7-418A http://orcid.org/0000-0001-8440-5299 0000-0001-8440-5299 Gano, Lurdes Gano, Lurdes https://www.ciencia-id.pt/C11F-51E3-6084 C11F-51E3-6084 http://orcid.org/0000-0001-7186-2060 0000-0001-7186-2060 Correia, Isabel Correia, Isabel https://www.ciencia-id.pt/1719-285A-843B 1719-285A-843B http://orcid.org/0000-0001-7096-4284 0000-0001-7096-4284 Correia, João D. G. Correia, João D. G. https://www.ciencia-id.pt/EC11-F3E9-78A2 EC11-F3E9-78A2 http://orcid.org/0000-0002-7847-4906 0000-0002-7847-4906 Casimiro, Sandra Casimiro, Sandra https://www.ciencia-id.pt/0F12-5181-0B22 0F12-5181-0B22 http://orcid.org/0000-0002-6917-4477 0000-0002-6917-4477 Costa, Luis Costa, Luis https://www.ciencia-id.pt/041E-4ADE-FB64 041E-4ADE-FB64 http://orcid.org/0000-0002-4782-7318 0000-0002-4782-7318 Santos, Isabel Cordeiro Santos, Isabel Cordeiro https://www.ciencia-id.pt/AC1E-5D38-26CA AC1E-5D38-26CA http://orcid.org/0000-0001-8350-480X 0000-0001-8350-480X Fernandes, Célia Fernandes, Célia https://www.ciencia-id.pt/3B1A-E650-A59E 3B1A-E650-A59E http://orcid.org/0000-0002-2119-8293 0000-0002-2119-8293 |
| publishDate | 2016 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
| service_str_mv | urn:repositoryAcronym:ul |
| spelling | engElsevierpt_PTWe aimed at exploring block copolymer micelles (BCMs) for the simultaneous delivery of radiation/chemotherapy to cancer cells. To achieve that goal, we have prepared and characterized a novel type of docetaxel (DTX) loaded and non-loaded BCMs. The micelles were decorated with pyrazolyl-diamine chelating units to stabilize the matched pair 99mTc/Re for image-guided delivery of therapeutic drugs. The in vitro studies have shown that DTX release is pH-dependent increasing at lower pH values. Anti-proliferative studies in different cancer cell lines showed that DTX-loaded BCMs present relevant anti-proliferative activity. In comparison to free DTX, the loaded-micelles exhibited higher anti-proliferative activity for the same DTX concentration, which mean that a similar therapeutic outcome may be achieved with reduced side effects. The pyrazolyl-diamine-functionalized micelles were labeled with fac-[99mTc(CO)3(H2O)3]+ in high radiochemical yield and purity. The radiolabeled micelles are stable in phosphate buffer and in cell culture media. Cellular uptake studies in different cancer cell lines indicate a cell type and time-dependent uptake, in agreement with the anti-proliferative activity. Early biodistribution studies in healthy BALB/c mice has shown prolonged circulation lifetime in the bloodstream and relevant in vivo stability, important features when considering an effective DTX delivery system and image-guided delivery agent for cancer theranostics.application/pdfpt_PTRadiolabeled block copolymer micelles for image-guided drug deliveryPersonalRibeiro, ElisabeteDSpacehttp://dspace.org/items/b7bfaebb-70cd-4e72-9aea-9f9c8599db2cDSpacehttp://dspace.org/items/b7bfaebb-70cd-4e72-9aea-9f9c8599db2cRibeiroElisabeteORCIDhttp://orcid.org0000-0001-8103-4744Researcher IDhttps://www.researcherid.comA-9552-2015PersonalAlho, IrinaDSpacehttp://dspace.org/items/ac30657e-6e0f-4437-8aea-bb1bcf05e1c5DSpacehttp://dspace.org/items/ac30657e-6e0f-4437-8aea-bb1bcf05e1c5DuarteIrinaCiência IDhttps://www.ciencia-id.pt651D-2E22-AB73ORCIDhttp://orcid.org0000-0002-3190-7479PersonalMarques, FernandaDSpacehttp://dspace.org/items/f8526a84-8c6b-4ab4-8dd8-e9a66ecc043cDSpacehttp://dspace.org/items/f8526a84-8c6b-4ab4-8dd8-e9a66ecc043cMarujo MarquesFernandaCiência IDhttps://www.ciencia-id.pt1C11-A0C7-418AORCIDhttp://orcid.org0000-0001-8440-5299Scopus Author IDhttps://www.scopus.com16402591700PersonalGano, LurdesDSpacehttp://dspace.org/items/032ea886-49b5-40c6-bb5f-5cb7db74efafDSpacehttp://dspace.org/items/032ea886-49b5-40c6-bb5f-5cb7db74efafBarrela Patricio GanoMaria LurdesCiência IDhttps://www.ciencia-id.ptC11F-51E3-6084ORCIDhttp://orcid.org0000-0001-7186-2060Scopus Author IDhttps://www.scopus.com8976995900PersonalCorreia, IsabelDSpacehttp://dspace.org/items/5918480b-dc55-4cc6-9b72-d53503665eb1DSpacehttp://dspace.org/items/5918480b-dc55-4cc6-9b72-d53503665eb1CorreiaIsabelCiência IDhttps://www.ciencia-id.pt1719-285A-843BORCIDhttp://orcid.org0000-0001-7096-4284Researcher IDhttps://www.researcherid.comH-7772-2012Scopus Author IDhttps://www.scopus.com7003557498Scopus Author IDhttps://www.scopus.com57217330156PersonalCorreia, João D. G.DSpacehttp://dspace.org/items/ffc14ae3-9775-41bf-a353-d7ded14bf152DSpacehttp://dspace.org/items/ffc14ae3-9775-41bf-a353-d7ded14bf152CorreiaJoãoCiência IDhttps://www.ciencia-id.ptEC11-F3E9-78A2ORCIDhttp://orcid.org0000-0002-7847-4906Researcher IDhttps://www.researcherid.comJ-7036-2013Scopus Author IDhttps://www.scopus.com7202364104PersonalCasimiro, SandraDSpacehttp://dspace.org/items/fd665de1-a7e6-4638-94c3-ecc645f84607DSpacehttp://dspace.org/items/fd665de1-a7e6-4638-94c3-ecc645f84607Cara de Anjo CasimiroSandra CristinaCiência IDhttps://www.ciencia-id.pt0F12-5181-0B22ORCIDhttp://orcid.org0000-0002-6917-4477Scopus Author IDhttps://www.scopus.com14043403400PersonalCosta, LuisDSpacehttp://dspace.org/items/8a2ab4c6-ba86-4433-b4b7-6256d81890e5DSpacehttp://dspace.org/items/8a2ab4c6-ba86-4433-b4b7-6256d81890e5CostaLuisCiência IDhttps://www.ciencia-id.pt041E-4ADE-FB64ORCIDhttp://orcid.org0000-0002-4782-7318PersonalSantos, Isabel CordeiroDSpacehttp://dspace.org/items/a48b4d98-ec02-44a6-b77d-447b293855f0DSpacehttp://dspace.org/items/a48b4d98-ec02-44a6-b77d-447b293855f0Cordeiro SantosIsabelCiência IDhttps://www.ciencia-id.ptAC1E-5D38-26CAORCIDhttp://orcid.org0000-0001-8350-480XPersonalFernandes, CéliaDSpacehttp://dspace.org/items/fb6db2b2-12f5-4491-a8b8-6b9ac1b72ba7DSpacehttp://dspace.org/items/fb6db2b2-12f5-4491-a8b8-6b9ac1b72ba7FernandesCéliaCiência IDhttps://www.ciencia-id.pt3B1A-E650-A59EORCIDhttp://orcid.org0000-0002-2119-8293HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptISSNIsPartOf0378-5173DOIIsPartOf10.1016/j.ijpharm.2016.11.0042022-02-21T17:44:24Z20162016-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/51440http://purl.org/coar/access_right/c_16ecrestricted access(99m)TcBlock copolymer micelleDrug delivery systemPEG-b-PCLRadiolabeled micelles1495441 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/188bbb0f-b943-4ad8-8dc1-430ebb6fd1a7/downloadInternational Journal of Pharmaceutics5151-2692701 |
| spellingShingle | Radiolabeled block copolymer micelles for image-guided drug delivery Ribeiro, Elisabete (99m)Tc Block copolymer micelle Drug delivery system PEG-b-PCL Radiolabeled micelles |
| status | SINGLETON |
| subject.fl_str_mv | (99m)Tc Block copolymer micelle Drug delivery system PEG-b-PCL Radiolabeled micelles |
| title | Radiolabeled block copolymer micelles for image-guided drug delivery |
| title_full | Radiolabeled block copolymer micelles for image-guided drug delivery |
| title_fullStr | Radiolabeled block copolymer micelles for image-guided drug delivery |
| title_full_unstemmed | Radiolabeled block copolymer micelles for image-guided drug delivery |
| title_short | Radiolabeled block copolymer micelles for image-guided drug delivery |
| title_sort | Radiolabeled block copolymer micelles for image-guided drug delivery |
| topic | (99m)Tc Block copolymer micelle Drug delivery system PEG-b-PCL Radiolabeled micelles |
| topic_facet | (99m)Tc Block copolymer micelle Drug delivery system PEG-b-PCL Radiolabeled micelles |
| url | http://hdl.handle.net/10451/51440 |
| visible | 1 |