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Anti-RhoJ antibody functionalized Au@I nanoparticles as CT-guided tumor vessel-targeting radiosensitizers in patient-derived tumor xenograft model

Liu, Sen, Li, Hui, Xia, Luyao, Xu, Peipei, Ding, Yin, Huo, Da, Hu, Yong
Biomaterials 2017 v.141 pp. 1-12
X-radiation, angiogenesis, antibodies, biocompatibility, computed tomography, cytokines, cytotoxicity, drug therapy, gold, hypoxia, iodine, irradiation, metastasis, models, nanoparticles, neoplasms, radiotherapy, relapse, vascular endothelial growth factors
The clinical success of radiotherapy is greatly hampered due to its intolerable off-target cytotoxicity induced by the high dose of radiation. Meanwhile, low dose of irradiation greatly potentiates the intratumoral angiogenesis, which promotes the local relapse and metastasis of tumor. Therefore, it is essential to reduce the irradiation dosage while inhibiting the tumor angiogenesis during radiotherapy. In this work, tumor vessel specific ultrafine Au@I nanoparticles (AIRA NPs) are fabricated and used as targeted radiosensitizers. Due to the presence of Au and iodine, these AIRA NPs exhibit superb X-ray attenuation for contrast-enhanced computed tomography (CT). Once injected, these AIRA NPs bind specifically to both newly formed tumor vessels in peri- and intratumoral regions and pre-existing tumor vessels. Upon radiation under CT guidance, AIRA NPs remarkably enhanced the killing efficacy against tumors in vivo with respect to radiation alone or anti-angiogenesis chemotherapy. Meanwhile, down-regulation of the level of circulating VEGF cytokine further indicates that our strategy can eradicate tumor without risking the recurrence of hypoxia and angiogenesis. Our demonstration provides a robust method of cancer therapy integrating good biocompatibility, high specificity and relapse-free manner alternative to traditional metal NPs enhanced radiotherapy.