Anti-EGFR Targeted Multifunctional I-131 Radio-Nanotherapeutic for Treating Osteosarcoma: In Vitro 3D Tumor Spheroid Model

The systemic delivery of doxorubicin (DOX) to treat osteosarcoma requires an adequate drug concentration to be effective, but in doing so, it raises the risk of increasing organ off-target toxicity and developing drug resistance. Herein, this study reveals a multiple therapeutic nanocarrier delivery platform that overcomes off-target toxicity by providing good specificity and imparting enhanced tumor penetration in a three-dimensional (3D) human MG-63 spheroid model. By synthesizing PEG-PLGA nanoparticles by the double emulsion method, encapsulating DOX and Na(131)I in the inner core, and conjugating with an epidermal growth factor receptor (EGFR) antibody, it is intended to specifically target human MG-63 cells. The nanocarrier is biocompatible with blood and has good stability characteristics. Na(131)I encapsulation efficiency was >96%, and radiochemical purity was >96% over 96 h. A DOX encapsulation efficacy of ~80% was achieved, with a drug loading efficiency of ~3%, and a sustained DOX release over 5 days. The nanocarrier EGFR antibody achieved a ~80-fold greater targeting efficacy to MG-63 cells (EGFR+) than fibroblast cells (EGFR−). The targeted multiple therapeutic DIE-NPs have a higher penetration and uptake of Na(131)I to the 3D model and a ~3-fold higher cytotoxicity than the DOX monotherapy (D-NPs). The co-administration of DOX and Na(131)I (DIE-NPs) disrupts DNA repair and generates free radicals resulting in DNA damage, triggering the activation of apoptosis pathways. This leads to inhibition of MG-63 cell proliferation and promotes cell cycle arrest in the G0/G1 phase. Furthermore, the PEGylated anti-EGFR functionalized DIE-NPs were found to be biocompatible with red blood cells and to have no adverse effects. This anti-EGFR targeted multifunctional I-131 radio-nanotherapeutic signifies a customizable specific targeted treatment for osteosarcoma.