Paclitaxel-loaded expansile nanoparticles improve survival following cytoreductive surgery in pleural mesothelioma xenografts
Paclitaxel-loaded expansile nanoparticles improve survival following cytoreductive surgery in pleural mesothelioma xenografts
复制标题
DOI：
10.1016/j.jtcvs.2019.12.076
复制
发表时间：
2020-09-01
影响因子：
6
通讯作者：
Colson, Yolonda L.
中科院分区：
文献类型：
--
作者：
Ngoc-Quynh Chu;Liu, Rong;Colson, Yolonda L.
Objective: Malignant pleural mesothelioma is a lethal malignancy with poor survival and high local recurrence rates despite multimodal therapy with cytoreduction and chemoradiation. We evaluated the antitumor efficacy of a paclitaxel-loaded pH responsive expansile nanoparticle (PTX-eNP) in 2 clinically relevant murine xenograft models of malignant pleural mesothelioma.Methods: Luciferase-transfected MSTO-211H human mesothelioma cells were injected into the thoracic cavity of immunodeficient Nu/J mice. Tumor burden was monitored by bioluminescent imaging. Animals were randomized into 2 models of disease treatment chemotherapy with PTX-eNPs alone delivered locally for early limited disease or cytoreductive surgery plus local PTX-eNP chemotherapy for advanced disease. Within each disease model, anti-tumor efficacy of PTX-eNP was compared against standard formulation paclitaxel and drug-empty nanoparticles. Influence on survival was calculated. Fluorescently labeled PTX-eNPs and immunohistochemistry evaluated in vivo drug localization to tumor.Results: Intrathoracic injection of MSTO-211H resulted in large tumor deposits distributed within the pleural space of the murine thoracic cavity. Local multidose treatment with PTX-eNPs alone in limited stage disease more than doubled survival compared with drug-empty nanoparticles (P
