Antibody functionalized targeted novel epigenetic nanotherapy for paediatric neuroblastoma

The neuroblastoma is the most heterogeneous, malignant, extracranial, childhood cancer of the embryonic sympathoadrenal lineage of the neural crest which mainly affect the adrenal glands. The polycomb protein, Bmi1, is highly expressed in the neuroblastoma tumorigenesis and executes epigenetic regulation of several downstream markers through its E3 ligase activity. The suppression of Bmi1 with a specific inhibitor, PRT4165, possesses a therapeutic potential but limitations such as off targeting impede its applications. In order to manifest Bmi1-specific targeted nanotherapy, PRT4165-encapsulated and anti-GD2-decorated (for active targeting of neuroblastoma) human serum albumin nanoparticles (PRT@HSANPs@GD2) are introduced as neuroblastoma therapy. PRT@HSANPs@GD2 enhance the cellular internalization and cytotoxicity through apoptosis in the GD2⁺ neuroblastoma cells. Furthermore, PRT@HSANPs@GD2 exhibit superior regression of tumor volumes, and downregulation of Bmi1. In addition, we report Bmi1 and Oct3/4 along with Oct3/4 and Vimentin interactions in neuroblastoma for the first-time wherein our nanoformulation, PRT@HSANPs@GD2, repress the Bmi1 and Oct3/4 along with Oct3/4 and Vimentin interactions in neuroblastoma. The GD2 targeting through nanoparticles-encapsulated with PRT4165 is an innovative and novel targeted nanotherapy regimen for the neuroblastoma with a future potential of translational development.