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Combining image-guided therapy techniques for the treatment of liver cancers is a strategy that is being used to improve local tumor control rates. Here, we evaluate the intratumoral uptake of nanoparticles used in combination with radiofrequency ablation (RFA), irreversible electroporation (IRE), or laser induced thermal therapy (LITT). Eight rabbits with VX2 tumor in the liver underwent one of four treatments: (i) nanoembolization (NE) with radiolabeled, hollow gold nanoparticles loaded with doxorubicin (⁶⁴Cu-PEG-HAuNS-DOX); (ii) NE + RFA; (iii) NE + IRE; (iv) NE +LITT. Positron emission tomography/computed tomography (PET/CT) imaging was obtained 1-hr or 18-hrs after intervention. Tissue samples were collected for autoradiography and transmission electron microscopy (TEM) analysis. PET/CT imaging at 1-hr showed focal deposition of oil and nanoparticles in the tumor only after NE+ RFA but at 18-hrs, all animals had focal accumulation of oil and nanoparticles in the tumor region. Autoradiograph analysis demonstrated nanoparticle deposition in the tumor and in the ablated tissues adjacent to the tumor when NE was combined with ablation. TEM results showed the intracellular uptake of nanoparticles in tumor only after NE + IRE. Nanoparticles demonstrated a structural change, suggesting direct interaction, potentially leading to drug release, only after NE + LITT. The findings demonstrate that a combined NE and ablation treatment technique for liver tumors is feasible, resulting in deposition of nanoparticles in and around the tumor. Depending on the ablative energy applied, different effects are seen on nanoparticle localization and structure. These effects should be considered when designing nanoparticles for use in combination with ablation technologies.

Imaging Intratumoral Nanoparticle Uptake After Combining Nanoembolization with Various Ablative Therapies in Hepatic VX2 Rabbit Tumors