Neuroblastoma (NB) is an embryonic tumor originating from the neural crest. The most well-defined genetic alteration in NB is the overexpression of the MYCN protein. PI3K/AKT/mTOR and AURORA signaling pathways play a role in MYCN stabilization, and abnormal activation of these pathways has been identified in NB. Nanoparticle (NP) drug delivery systems targeting tumor cells directly assist in the combined delivery of agents and reducing toxicity. In this study, the aim was to develop NPs that reduce the activity of mTOR and AURORA pathways, potentially decreasing MYCN protein enhancement and stability, by combining inhibitors and targeting them specifically to the tumor, and to demonstrate their effect in NB. Everolimus (EVER) and tozasertib (TOZA) encapsulated in NP and targeted with dinutuximab β (DTX-β). Experiments including viability, apoptosis, gene and protein expression determination were performed. DTX-β/EVER + TOZA@PEG-b(block)-PLGA NPs were successful to reduce the cell viability and to increase apoptosis. In vivo studies demonstrated notable tumor growth inhibition without organ toxicity. Elevated caspase expression and suppressed proteins indicated enhanced apoptosis and reduced oncogenic activity. DTX-β/EVER-TOZA@PEG-b-PLGA may exert cytotoxic and apoptotic effects in NB. The use of targeted nanocarriers in NB treatment may enhance cytotoxic and apoptotic responses specifically in the tumor region.
Gökbayrak et al. (Thu,) studied this question.