Combined Replenishment of miR ‐34a and let‐7b by Targeted Nanoparticles Inhibits Tumor Growth in Neuroblastoma Preclinical Models

Targeted nanocarriers entrapping microRNAs (miRNA) ‐mimics are selectively delivered to neuroblastoma cells. The technology exploits the nucleic acids negative charges to build coated cationic liposomes, which are functionalized with antibodies against GD2 receptor. The combined replenishment of miR ‐34a and let‐7b by neuroblastoma‐targeted nanoparticles exerts a cooperative down‐modulation of key oncogenes. The reactivated regulatory networks lead to a favorable therapeutic response in preclinical models. AbstractNeuroblastoma (NB) tumor substantially contributes to childhood cancer mortality. The design of novel drugs targeted to specific molecular alterations becomes mandatory, especially for high ‐risk patients burdened by chemoresistant relapse. The dysregulated expression ofMYCN,ALK, andLIN28B and the diminished levels of miR ‐34a and let‐7b are oncogenic in NB. Due to the ability of miRNA‐mimics to recover the tumor suppression functions of miRNAs underexpressed into cancer cells, safe and efficient nanocarriers selectively targeted to NB cells and tested in clinically relevant mouse models are developed. The tech nology exploits the nucleic acids negative charges to build coated‐cationic liposomes, then functionalized with antibodies against GD2 receptor. The replenishment of miR ‐34a and let‐7b by NB‐targeted nanoparticles, individually and more powerfully in combination, significantly reduces cell division, proliferation, neoangiogenesis, t...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research