Antibody-Targeted Bismuth Gadolinium Nanoconjugate for Image-Guided Radiotherapy of Hepatocellular Carcinoma

作者：Mishra A, San Valentin EMD, Barcena AJR, Bolinas DKM, Bernardino MR, Canlas G, Ricks KA, Damasco JA, Melancon MP · 发表于：ACS applied materials & interfaces · 年份：2025 · DOI：10.1021/acsami.4c21949 · 研究领域：bismuth gadolinium nanoparticles、hepatocellular carcinoma、image-guided radiation therapy、nanoconjugate、theranostic agents、vascular endothelial growth factor

Hepatocellular carcinoma (HCC), one of the most lethal cancers of the liver, has limited treatment options at advanced stages. Here, bismuth gadolinium (BiGd) nanoparticles (NPs) conjugated with anti-vascular endothelial growth factor antibody (aVEGF) are designed and tested for targeted image-guided radiation therapy against HCC. The BiGd NPs are synthesized using the sol-gel technique, functionalized with silica NPs, and labeled with fluorescent protamine-rhodamine B. For tumor targeting, the NPs are conjugated with aVEGF, and an in vitro study confirms the binding of the aVEGF-BiGd nanoconjugate to McA-RH7777 hepatoma cells. Biocompatibility of the aVEGF-BiGd nanoconjugate is evaluated using McA-RH7777 cells, with no cytotoxicity observed even at 250 μg/mL. Also, aVEGF-BiGd demonstrates in vivo microcomputed tomography contrast enhancement. NPs and/or radiation therapy (RT) is conducted in female BALB/c nude mice with subcutaneously implanted McA-RH7777 cells, and a significant reduction in tumor size is observed in the mice treated with the aVEGF-BiGd nanoconjugate and RT compared to other groups (p < 0.01). The combined effect of nanoconjugate and RT exhibits decreased vascularity, cell proliferation, and increased apoptosis. This study demonstrates the potential of the developed hybrid BiGd nanoconjugate for targeted and image-guided radiotherapy of HCC.