title: Prevention of nodal metastases in breast cancer following the lymphatic migration of paclitaxel-loaded expansile nanoparticles.
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.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Denis M
authors.initials: DM
authors.lastname: Gilmore
authors.forename: Kimberly Ann V
authors.initials: KA
authors.lastname: Zubris
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Xu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Catalano
authors.forename: Robert F
authors.initials: RF
authors.lastname: Padera
authors.forename: Mark W
authors.initials: MW
authors.lastname: Grinstaff
authors.forename: Yolonda L
authors.initials: YL
authors.lastname: Colson
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel