Noninvasive radiofrequency field destruction of pancreatic adenocarcinoma xenografts treated with targeted gold nanoparticles.
Noninvasive radiofrequency field destruction of pancreatic adenocarcinoma xenografts treated with targeted gold nanoparticles.
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DOI：
10.1158/1078-0432.ccr-10-2055
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Curley SA
中科院分区：
文献类型：
--
作者：
Glazer ES;Zhu C;Massey KL;Thompson CS;Kaluarachchi WD;Hamir AN;Curley SA
Pancreatic carcinoma is one of the deadliest cancers with few effective treatments. Gold nanoparticles (AuNPs) are potentially therapeutic because of the safety demonstrated thus far and their physio-chemical characteristics. We utilized the astounding heating rates of AuNPs in nonionizing radiofrequency (RF) radiation to investigate human pancreatic xenograft destruction in a murine model. Weekly, Panc-1 and Capan-1 human pancreatic carcinoma xenografts in immunocompromised mice were exposed to an RF field 36 hours after treatment (intraperitoneal) with cetuximab or PAM4 antibody conjugated AuNPs, respectively. Tumor sizes were measured weekly while necrosis and cleaved caspase-3 were investigated with H&E staining and immunofluorescence, respectively. In addition, AuNP internalization and cytotoxicity were investigated in vitro with confocal microscopy and flow cytometry, respectively. Panc-1 cells demonstrated increased apoptosis with decreased viability after treatment with cetuximab conjugated AuNPs and RF field exposure (p = 0.00005). Differences in xenograft volumes were observed within 2 weeks of initiating therapy. Cetuximab-conjugated and PAM4-conjugated AuNPs demonstrated RF field-induced destruction of Panc-1 and Capan-1 pancreatic carcinoma xenografts after six weeks of weekly treatment (p = 0.004 and p = 0.035, respectively). There was no evidence of injury to murine organs. Cleaved caspase-3 and necrosis were both increased in treated tumors. This study demonstrates a potentially novel cancer therapy by non-invasively inducing intracellular hyperthermia with targeted AuNPs in an RF field. While the therapy is dependent on the specificity of the targeting antibody, normal tissues were without toxicity despite systemic therapy and whole body RF field exposure.
