Prevention of nodal metastases in breast cancer following the lymphatic migration of paclitaxel-loaded expansile nanoparticles.
Prevention of nodal metastases in breast cancer following the lymphatic migration of paclitaxel-loaded expansile nanoparticles.
复制标题
DOI：
10.1016/j.biomaterials.2012.11.038
复制
发表时间：
2013-02
期刊：
影响因子：
14
通讯作者：
Colson, Yolonda L.
中科院分区：
文献类型：
--
作者：
Liu, Rong;Gilmore, Denis M.;Zubris, Kimberly Ann V.;Xu, Xiaoyin;Catalano, Paul J.;Padera, Robert F.;Grinstaff, Mark W.;Colson, Yolonda L.
虽然有局限性病变的乳腺癌患者显示出良好的长期预后，但高达40%的单独接受局部切除的患者可能存在隐匿性淋巴结转移疾病，导致局部复发增加和生存率下降。考虑到靶向给药有可能导致更有效的局部区域控制和更少的发病率，目前的研究评估了载药聚合物可膨胀纳米粒(ENP)从肿瘤部位迁移到区域淋巴结、局部输送化疗有效载荷以及防止原发肿瘤生长和淋巴结转移的能力。可膨胀的纳米粒子进入肿瘤细胞，紫杉醇ENP(Pax-ENP)在体外表现出剂量依赖性的细胞毒性，在显微镜下和已建立的小鼠乳腺癌模型中，显著降低了体内对人三阴性乳腺癌的肿瘤倍增时间。此外，Pax-ENP转移到腋窝淋巴结导致结内紫杉醇浓度较高，淋巴结转移率显著降低。这些发现表明，载药ENP的淋巴迁移提供了区域靶向的化疗，既减少了局部肿瘤的生长，又战略性地防止了区域肿瘤引流淋巴盆地内的淋巴结转移的发展。
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.
登录
查看更多内容
DOI：
10.1186/bcr1026
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Jenkins DE;Hornig YS;Oei Y;Dusich J;Purchio T
通讯作者：
Purchio T
影响因子：
15
作者：
Griset, Aaron P.;Walpole, Joseph;Grinstaff, Mark W.
通讯作者：
Grinstaff, Mark W.
影响因子：
14
作者：
Colson, Yolonda L.;Liu, Rong;Grinstaff, Mark W.
通讯作者：
Grinstaff, Mark W.
影响因子：
51.1
作者：
Krag, David N.;Anderson, Stewart J.;Julian, Thomas B.;Brown, Ann M.;Harlow, Seth P.;Costantino, Joseph P.;Ashikaga, Takamaru;Weaver, Donald L.;Mamounas, Eleftherios P.;Jalovec, Lynne M.;Frazier, Thomas G.;Noyes, R. Dirk;Robidoux, Andre;Scarth, Hugh M. C.;Wolmark, Norman
通讯作者：
Wolmark, Norman
大型动物模型中的纳米颗粒迁移和紫杉醇向区域淋巴结的递送。
DOI：
10.1016/j.jamcollsurg.2011.11.006
发表时间：
2012-03
影响因子：
5.2
作者：
Khullar, Onkar V.;Griset, Aaron P.;Gibbs-Strauss, Summer L.;Chirieac, Lucian R.;Zubris, Kimberly A. V.;Frangioni, John V.;Grinstaff, Mark W.;Colson, Yolonda L.
通讯作者：
Colson, Yolonda L.