Multifunctional Nanoparticles for Multimodal Imaging-Guided Low-Intensity Focused Ultrasound/Immunosynergistic Retinoblastoma Therapy

Retinoblastoma (RB) is prone to delayed diagnosis or treatment and has an increased likelihood of metastasizing. Thus, it is crucial to perform an effective imaging examination and provide optimal treatment of RB to prevent metastasis. Nanoparticles that support diagnostic imaging and targeted therapy are expected to noninvasively integrate tumor diagnosis and treatment. Herein, we report a multifunctional nanoparticle for multimodal imaging-guided low-intensity focused ultrasound (LIFU)/immunosynergistic RB therapy. Magnetic hollow mesoporous gold nanocages (AuNCs) conjugated with Fe3O4 nanoparticles (AuNCs-Fe3O4) were prepared to encapsulate muramyl dipeptide (MDP) and perfluoropentane (PFP). The multimodal imaging capabilities, antitumor effects, and dendritic cell (DC) activation capacity of these nanoparticles combined with LIFU were explored in vitro and in vivo. The biosafety of AuNCs-Fe3O4/MDP/PFP was also evaluated systematically. The multifunctional magnetic nanoparticles enhanced photoacoustic (PA), ultrasound (US), and magnetic resonance (MR) imaging in vivo and in vitro, which was helpful for diagnosis and efficacy evaluation. Upon accumulation in tumors via a magnetic field, the nanoparticles underwent phase transition under LIFU irradiation and MDP was released. A combined effect of AuNCs-Fe3O4/MDP/PFP and LIFU was recorded and verified. AuNCs-Fe3O4/MDP/PFP enhanced the therapeutic effect of LIFU and led to direct apoptosis/necrosis of tumors, while MDP promoted DC maturation and activation and activated the ability of DCs to recognize and clear tumor cells. By enhancing PA/US/MR imaging and inhibiting tumor growth, the multifunctional AuNC-Fe3O4/MDP/PFP nanoparticles show great potential for multimodal imaging-guided LIFU/immunosynergistic therapy of RB. The proposed nanoplatform facilitates cancer theranostics with high biosafety.