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

Molecular Cancer Therapeutics
Sharon M SagnellaMaria Kavallaris

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 apo...Continue Reading

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Citations

Apr 2, 2019·Thyroid : Official Journal of the American Thyroid Association·Lauren Jin Suk JooStan B Sidhu
Sep 10, 2020·BMC Biomedical Engineering·Kimberly J Ornell, Jeannine M Coburn
Sep 29, 2019·Seminars in Cancer Biology·Faheem Hyder PottooMohammad Amjad Kamal
Jan 25, 2021·Advanced Drug Delivery Reviews·Taskeen Iqbal JanjuaAmirali Popat
Jun 3, 2021·International Journal of Molecular Sciences·Mariam ElshiatyPetros Christopoulos
Nov 27, 2021·Current Protocols·Andrew J GiffordMichelle Haber

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