Prevention of nodal metastases in breast cancer following the lymphatic migration of paclitaxel-loaded expansile nanoparticles
Identifieur interne : 005416 ( Ncbi/Checkpoint ); précédent : 005415; suivant : 005417Prevention of nodal metastases in breast cancer following the lymphatic migration of paclitaxel-loaded expansile nanoparticles
Auteurs : Rong Liu [États-Unis] ; Denis M. Gilmore [États-Unis] ; Kimberly Ann V. Zubris [États-Unis] ; Xiaoyin Xu [États-Unis] ; Paul J. Catalano [États-Unis] ; Robert F. Padera [États-Unis] ; Mark W. Grinstaff [États-Unis] ; Yolonda L. Colson [États-Unis]Source :
- Biomaterials [ 0142-9612 ] ; 2012.
Abstract
Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, up to 40% of patients treated with local resection alone may harbor occult nodal metastatic disease leading to increased locoregional recurrence and decreased survival. Given the potential for targeted drug delivery to result in more efficacious locoregional control with less morbidity, the current study assessed the ability of drug-loaded polymeric expansile nanoparticles (eNP) to migrate from the site of tumor to regional lymph nodes, locally deliver a chemotherapeutic payload, and prevent primary tumor growth as well as lymph node metastases. Expansile nanoparticles entered tumor cells and paclitaxel-loaded eNP (Pax-eNP) exhibited dose-dependent cytotoxicity in vitro and significantly decreased tumor doubling time in vivo against human triple negative breast cancer in both microscopic and established murine breast cancer models. Furthermore, migration of Pax-eNP to axillary lymph nodes resulted in higher intranodal paclitaxel concentrations and a significantly lower incidence of lymph node metastases. These findings demonstrate that lymphatic migration of drug-loaded eNP provides regionally targeted delivery of chemotherapy to both decrease local tumor growth and strategically prevent the development of nodal metastases within the regional tumor-draining lymph node basin.
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DOI: 10.1016/j.biomaterials.2012.11.038
PubMed: 23228419
PubMed Central: 3541056
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Padera</name><affiliation wicri:level="1"><nlm:aff id="A5">Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115</wicri:regionArea><wicri:noRegion>MA 02115</wicri:noRegion></affiliation></author><author><name sortKey="Grinstaff, Mark W" sort="Grinstaff, Mark W" uniqKey="Grinstaff M" first="Mark W." last="Grinstaff">Mark W. Grinstaff</name><affiliation wicri:level="1"><nlm:aff id="A2">Departments of Biomedical Engineering and Chemistry, Boston University, Boston, MA 02215, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Departments of Biomedical Engineering and Chemistry, Boston University, Boston, MA 02215</wicri:regionArea><wicri:noRegion>MA 02215</wicri:noRegion></affiliation></author><author><name sortKey="Colson, Yolonda L" sort="Colson, Yolonda L" uniqKey="Colson Y" first="Yolonda L." last="Colson">Yolonda L. Colson</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.</nlm:aff><country xml:lang="fr" wicri:curation="lc">États-Unis</country><wicri:regionArea>Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115</wicri:regionArea><wicri:noRegion>MA 02115</wicri:noRegion></affiliation></author></analytic><series><title level="j">Biomaterials</title><idno type="ISSN">0142-9612</idno><idno type="eISSN">1878-5905</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Although breast cancer patients with localized disease exhibit an excellent long-term prognosis, up to 40% of patients treated with local resection alone may harbor occult nodal metastatic disease leading to increased locoregional recurrence and decreased survival. Given the potential for targeted drug delivery to result in more efficacious locoregional control with less morbidity, the current study assessed the ability of drug-loaded polymeric expansile nanoparticles (eNP) to migrate from the site of tumor to regional lymph nodes, locally deliver a chemotherapeutic payload, and prevent primary tumor growth as well as lymph node metastases. Expansile nanoparticles entered tumor cells and paclitaxel-loaded eNP (Pax-eNP) exhibited dose-dependent cytotoxicity in vitro and significantly decreased tumor doubling time in vivo against human triple negative breast cancer in both microscopic and established murine breast cancer models. Furthermore, migration of Pax-eNP to axillary lymph nodes resulted in higher intranodal paclitaxel concentrations and a significantly lower incidence of lymph node metastases. These findings demonstrate that lymphatic migration of drug-loaded eNP provides regionally targeted delivery of chemotherapy to both decrease local tumor growth and strategically prevent the development of nodal metastases within the regional tumor-draining lymph node basin.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Liu, Rong" sort="Liu, Rong" uniqKey="Liu R" first="Rong" last="Liu">Rong Liu</name></noRegion><name sortKey="Catalano, Paul J" sort="Catalano, Paul J" uniqKey="Catalano P" first="Paul J." last="Catalano">Paul J. Catalano</name><name sortKey="Colson, Yolonda L" sort="Colson, Yolonda L" uniqKey="Colson Y" first="Yolonda L." last="Colson">Yolonda L. Colson</name><name sortKey="Gilmore, Denis M" sort="Gilmore, Denis M" uniqKey="Gilmore D" first="Denis M." last="Gilmore">Denis M. Gilmore</name><name sortKey="Grinstaff, Mark W" sort="Grinstaff, Mark W" uniqKey="Grinstaff M" first="Mark W." last="Grinstaff">Mark W. Grinstaff</name><name sortKey="Padera, Robert F" sort="Padera, Robert F" uniqKey="Padera R" first="Robert F." last="Padera">Robert F. Padera</name><name sortKey="Xu, Xiaoyin" sort="Xu, Xiaoyin" uniqKey="Xu X" first="Xiaoyin" last="Xu">Xiaoyin Xu</name><name sortKey="Zubris, Kimberly Ann V" sort="Zubris, Kimberly Ann V" uniqKey="Zubris K" first="Kimberly Ann V." last="Zubris">Kimberly Ann V. Zubris</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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