Nanoparticle Migration and Delivery of Paclitaxel to Regional Lymph Nodes in a Large Animal Model

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• 作者：Onkar V. Khullar ; MD^a ; Aaron P. Griset ; PhD^d ; Summer L. Gibbs-Strauss ; PhD^c ; Lucian R. Chirieac ; MD^b ; Kimberly A.V. Zubris ; BS^d ; John V. Frangioni ; MD ; PhD^c ; Mark W. Grinstaff ; PhD^d ; Yolonda L. Colson ; MD ; FACS^a ; ^{ycolson@partners.org}
• 关键词：C-eNP ; coumarin-conjugated expansile polymer nanoparticles ; eNP ; expansile polymer nanoparticles ; LN ; lymph nodes ; NIR ; near infrared ; OGpax-eNP ; Oregon Green paclitaxel-loaded expansile polymer nanoparticles ; PLGA ; poly (lactic-co-glycolic acid) ; SLN ; se
• 刊名：Journal of the American College of Surgeons
• 出版年：2012
• 出版时间：March, 2012
• 年：2012
• 卷：214
• 期：3
• 页码：328-337
• 全文大小：2708 K

文摘

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Background

The aim of this study was 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.

Study Design

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 used to identify intralymphatic migration of NIR-nanoparticles to draining inguinal or mesenteric LN after injection in swine hind legs or intestine. Nanoparticle-mediated intranodal delivery of chemotherapy was subsequently assessed with Oregon Green paclitaxel-loaded NIR-eNP (NIR-OGpax-eNP).

Results

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 after intradermal injection in the hind leg 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 and was 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.

Conclusions

Regionally-targeted intranodal chemotherapy can be delivered to draining LNs for both skin and solid organs using 50-nm paclitaxel-loaded eNP.