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Pubmed ID :29491149
Publication Date : //

Targeted Doxorubicin-Loaded Bacterially Derived Nano-Cells for the Treatment of Neuroblastoma.


Advanced stage neuroblastoma is an aggressive disease with limited treatment options for patients with drug-resistant tumors. Targeted delivery of chemotherapy for pediatric cancers offers promise to improve treatment efficacy and reduce toxicity associated with systemic chemotherapy. The EnGeneIC Dream Vector (EDV) is a nanocell, which can package chemotherapeutic drugs and target tumors via attachment of bispecific proteins to the surface of the nanocell. Phase I trials in adults with refractory tumors have shown an acceptable safety profile. Herein we investigated the activity of EGFR-targeted and doxorubicin-loaded EDV (EDV) for the treatment of neuroblastoma. Two independent neuroblastoma cell lines with variable expression of EGFR protein [SK-N-BE(2), high; SH-SY-5Y, low] were used. EDV induced apoptosis in these cells compared to control, doxorubicin, or non-doxorubicin loaded EDV In three-dimensional tumor spheroids, imaging and fluorescence life-time microscopy revealed that EDV had a marked enhancement of doxorubicin penetration compared to doxorubicin alone, and improved penetration compared to non-EGFR-targeted EDV, with enhanced spheroid penetration leading to increased apoptosis. In two independent orthotopic human neuroblastoma xenograft models, short-term studies (28 days) of tumor-bearing mice led to a significant decrease in tumor size in EDV-treated animals compared to control, doxorubicin, or non-EGFR EDV There was increased TUNEL staining of tumors at day 28 compared to control, doxorubicin, or non-EGFR EDV Moreover, overall survival was increased in neuroblastoma mice treated with EDV ( < 0007) compared to control. Drug-loaded bispecific-antibody targeted EDVs offer a highly promising approach for the treatment of aggressive pediatric malignancies such as neuroblastoma. .

Authors : Sagnella Sharon M , Trieu Jennifer , Brahmbhatt Himanshu , MacDiarmid Jennifer A , MacMillan Alex , Whan Renee M , Fife Christopher M , McCarroll Joshua A , Gifford Andrew J , Ziegler David S , Kavallaris Maria ,

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