In the past decade, there has been considerable interest in radiosensitization using gold nanoparticles that accumulate specifically in cancerous tissue while sparing normal tissues. Despite this interest, it remains unclear which nanoparticle morphologies, cellular uptake, or cytoplasmic distribution elicit optimal radiosensitization. We introduce gold nanotriangles (AuNTs) as a possible X-ray radiotherapy sensitizer. In this study, we first explored a large-scale synthetic method for the production of high quality monodisperse AuNTs. Second, we conducted in vitro and in vivo experiments to evaluate the effect of PEGylated AuNTs (pAuNTs) on cellular uptake, cytotoxicity, bio-distribution, and radiosensitization on radiation-resistant human Glioblastoma Multiforme (GBM) cells. Our results suggest that the new scale up synthesis methodology consistently produced high quality AuNTs and pAuNTs which had nonspecific cellular uptake without any obvious cytotoxicity and exhibited excellent radiosensitization.
Theoretical investigations suggest that gold nanoparticle (GNP)-mediated radiation dose enhancement and radiosensitization can be maximized when photons interact with gold, predominantly via photoelectric absorption. This makes ytterbium (Yb)-169, which emits photons with an average energy of 93 keV (just above the K-edge of gold), an ideal radioisotope for such purposes. This investigation tests the feasibility of tumor-specific prostate brachytherapy achievable with Yb-169 and actively targeted GNPs, using an external beam surrogate of Yb-169 created from an exotic filter material - erbium (Er) and a standard copper-filtered 250 kVp beam. The current in vitro study shows that treatment of prostate cancer cells with goserelin-conjugated gold nanorods (gGNRs) promotes gonadotropin releasing hormone receptor-mediated internalization and enhances radiosensitivity to both Er-filtered and standard 250 kVp beams, 14 and 10%, respectively. While the degree of GNP-mediated radiosensitization as seen from the in vitro study may be considered moderate, the current in vivo study shows that gGNR treatment plus Er-filtered x-ray irradiation is considerably more effective than radiation treatment alone (p < 0.0005), resulting in a striking reduction in tumor volume (50% smaller) 2 months following treatment. Overall, the current results provide strong evidence for the feasibility of tumor-specific prostate brachytherapy with Yb-169 and gGNRs.
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