Integration of gold nanodendrites and immune checkpoint blockers to achieve highly efficient photothermal immunotherapy for eradicating primary and distant metastatic osteosarcoma

Abstract

One of the challenges in immunotherapy is the difficulty for immune checkpoint blockers to seek and destruct ‘cold’ tumors. Here we tackled this challenge using a new nanomaterial with the capability of tumor targeting, photoablation, and immune checkpoint blocking, leading to successful eradication of primary and distant metastatic tumors by photothermal immunotherapy. Specifically, the programmed death receptor 1 antibody (aPD-1) was grafted onto novel Au nanodendrites (AuNDs) to prepare a complex (AuNDs@aPD-1). The dendritic structure of AuNDs@aPD-1 enabled sustained release of aPD-1 for blocking immune checkpoints and effective photoablation upon near-infrared irradiation for making tumors ‘hot’. Using osteosarcoma (OS) as a model ‘cold’ tumor, we found that intravenous injection of AuNDs@aPD-1, followed by near-infrared irradiation only on the primary tumor, destroyed primary and distant metastatic OS via activating T cells and blocking PD-1/programmed death-ligand 1 axis. The photothermal immunotherapy led to tumor eradication with a prolonged survival of mice and exhibited long-term immune memory to prevent tumor reinvasion and recurrence. AuNDs@aPD-1 presented good tumor-targeting ability due to a combination of nanomaterials-based passive targeting and antibody-enabled active targeting and thus was excreted in the blood circulation through a special hepatointestinal pathway. Hence, the AuNDs@aPD-1 is a promising biomaterial for treating metastatic OS through photothermal immunotherapy.