Nanoparticle migration and delivery of Paclitaxel to regional lymph nodes in a large animal model.
Nanoparticle migration and delivery of Paclitaxel to regional lymph nodes in a large animal model.
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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
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发表时间：
2012-03
影响因子：
5.2
通讯作者：
Colson, Yolonda L.
中科院分区：
文献类型：
--
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.
目的：利用可膨胀聚合物纳米粒(ENP)给药系统，在大型动物模型中证明向区域淋巴结(LN)进行迁移和原位化疗给药的可行性。通过将IR-813近红外(NIR)荧光染料包裹在香豆素偶联可膨胀聚合物纳米粒(NIR-C-ENP)中，制备了50 nm和100 nm双标记ENP。近红外成像和荧光显微镜被用来鉴定近红外纳米颗粒在猪的后腿或肠内注射后，向引流的腹股沟或肠系膜LN的淋巴管内迁移。随后用俄勒冈州绿色紫杉醇负载的NIR-ENP(NIR-OGpax-ENP)评估纳米颗粒介导的结内给药。NIR成像显示NIR-C-ENP和NIR-OGpax-ENP在后腿皮内注射或肠内浆膜下注射后，淋巴管直接迁移到引流区域的淋巴结节50 nm，而不是100 nm。荧光显微镜显示，用于近红外实时转运的IR-813与香豆素标记的聚合物和紫杉醇化疗共存于引流的淋巴结的包膜下空间内。这些研究证实了纳米粒子和包裹的有效载荷的结节迁移，并证实了将化疗药物直接集中到区域结节的可行性。使用50 nm紫杉醇载药的ENP可将局部靶向结内化疗输送到皮肤和实体器官的引流淋巴结。
To demonstrate feasibility of migration and in situ chemotherapy delivery to regional lymph nodes (LN) in a large animal model using an expansile polymer nanoparticle (eNP) delivery system. Dual-labeled 50 nm and 100 nm eNP were prepared by encapsulating an IR-813 near-infrared (NIR) fluorescent dye within coumarin-conjugated expansile polymer nanoparticles (NIR-C-eNP). NIR imaging and fluorescent microscopy were utilized to identify intralymphatic migration of NIR-nanoparticles to draining inguinal or mesenteric LN following injection in swine hindlegs or intestine. Nanoparticle-mediated intranodal delivery of chemotherapy was subsequently assessed with Oregon Green paclitaxel-loaded NIR-eNP (NIR-OGpax-eNP). NIR imaging demonstrated direct lymphatic migration of 50 nm, but not 100 nm, NIR-C-eNP and NIR-OGpax-eNP to the draining regional LNs following intradermal injection in the hindleg or subserosal injection in intestine. Fluorescent microscopy demonstrated that IR-813 used for NIR real-time trafficking colocalized with both the coumarin-labeled polymer and paclitaxel chemotherapy identified within the subcapsular spaces of the draining LNs. These studies verify nodal migration of both nanoparticle and encapsulated payload, and confirm the feasibility of focusing chemotherapy delivery directly to regional nodes. Regionally-targeted intranodal chemotherapy can be delivered to draining LNs for both skin and solid organs using 50 nm paclitaxel-loaded eNP.
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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：
9
作者：
Morton, DL;Cochran, AJ;Wang, HJ
通讯作者：
Wang, HJ
影响因子：
3
作者：
Lu, Hongxia;Li, Bin;Xu, Congjian
通讯作者：
Xu, Congjian
影响因子：
3.4
作者：
Murray, CA;Leong, WL;Ghazarian, DM
通讯作者：
Ghazarian, DM
影响因子：
14
作者：
Colson, Yolonda L.;Liu, Rong;Grinstaff, Mark W.
通讯作者：
Grinstaff, Mark W.