Evaluation of a nanomedicine-based drug delivery system for oral cancer lung metastasis treatment

Datum

29.07.2019

Zeit

11:00 - 12:00

Sprecher

Sabrina Marcazzan

Zugehörigkeit

University Hospital Essen, Germany & University of Milan, Italy

Sprache

en

Hauptthema

Biologie

Host

Marino Zerial

Beschreibung

Oral Squamous Cell Carcinoma (OSCC) is the sixth most common cancer worldwide and is still a fatal disease, with a 5-year survival rate of 25-40% in the presence of lymph node and distant metastases. In these cases, few therapeutic options are currently available. Recently, an injec-table nanoparticle generator (iNPG) loaded with polymeric doxorubicin (pDox) has been develo-ped by the Department of Nanomedicine, Houston Methodist Research Institute and reported promising results against lung metastasis. The aim of the present study was to evaluate the cy-totoxic effect of pDox nanoparticles (NPs) in metastatic OSCC cell lines and to develop relevant animal models of OSCC lung metastasis for further in vivo studies. The highly metastatic HSC-3 cell line (JCRB0623) and a novel cell line isolated from GFP/luciferase-transfected HSC-3-lung metastases reproduced in vivo were used. Cellular viability was evaluated after 72 and 96 h of treatment with pDox NPs and free form of doxorubicin by MTS assay and the nuclear localization of doxorubicin was visualized after 6 and 24 h by confocal microscopy. In addition, two xenograft mouse models of OSCC metastasis were developed using HSC-3 and HSC-3 M1 cells. The growth of the primary tumor and/or metastasis was evaluated by in vivo imaging and histology. Despite the minor cytotoxicity of pDox NPs compared with the free form of doxorubicin, the high-est concentrations of pDox NPs (0.5 and 1 µM) were able to effectively kill both HSC-3 and HSC-3 M1 cells. At the confocal microscopy, a delayed localization of doxorubicin into the nuclei was observed in the cells treated with pDox NPs compared with those treated with the free form of doxorubicin. In vivo, lung metastases and lymph node metastases were observed in the or-thotopic model of OSCC using GFP/luciferase HSC-3 cells, while only lung metastases were ob-served after the injection of GFP-sorted HSC-3 M1 cells into the tail vein. In conclusion, the ani-mal models of OSCC lung metastasis here reported may be used to validate in vivo the lower toxicity of pDox than doxorubicin observed in vitro.

Letztmalig verändert: 30.07.2019, 00:09:13