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Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery
Published on: June 23, 2020
Targeted Doxorubicin-Loaded Bacterially Derived Nano-Cells for the Treatment of Neuroblastoma
Sharon M Sagnella1,2,3, Jennifer Trieu1,2, Himanshu Brahmbhatt3
1Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Abstract:
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 (EDVTM) 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 EDVTM (EGFREDVTMDox) 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. EGFREDVTMDox induced apoptosis in these cells compared to control, doxorubicin, or non-doxorubicin loaded EGFREDVTM In three-dimensional tumor spheroids, imaging and fluorescence life-time microscopy revealed that EGFREDVTMDox had a marked enhancement of doxorubicin penetration compared to doxorubicin alone, and improved penetration compared to non-EGFR-targeted EDVTMDox, 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 EGFREDVTMDox-treated animals compared to control, doxorubicin, or non-EGFR EDVTMDox There was increased TUNEL staining of tumors at day 28 compared to control, doxorubicin, or non-EGFR EDVTMDox Moreover, overall survival was increased in neuroblastoma mice treated with EGFREDVTMDox (P < 0007) compared to control. Drug-loaded bispecific-antibody targeted EDVsTM offer a highly promising approach for the treatment of aggressive pediatric malignancies such as neuroblastoma. Mol Cancer Ther; 17(5); 1012-23. ©2018 AACR.
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