Abstract P3-12-13: Radiation enhancement with cysteine coated platinum nanoparticles

Abstract Background: Radiation is the current choice treatment for non-operable metastatic breast-brain cancer. When cancer lesions are located in sensitive areas like the brain or have excessive amounts of metastatic sites, radiation usually proves to be a more viable option than excision. Ionizing (X-ray and gamma) radiation is non-selective and affects all the tissue it penetrates. In order to concentrate the dose on tumors, high energy radiation from multiple directions is typically used, reaching the highest dose where the radiation crosses. This type of multiple angle treatment minimizes the dose to normal tissue by increasing overall normal tissue irradiation. The objective is to achieve sufficient radiation in the tumor tissue to cause the DNA strands to break and to disrupt the reproduction and maintenance of cancer cells while keeping the damage to normal tissue in a reasonable range for tissue preservation. Metal nanoparticles have shown promising results for reinforcing the radiation dose effect. High atomic number (Z) elements absorb a greater amount of radiation because the higher density raises the probability of interaction. The metal nanoparticles interact with the energy of the ionizing radiation by either scattering or absorbing, or accumulating the energy, thus increasing the number of DNA strand breaks in the nucleus of cells. Methods: Four breast cancer cell lines (BT-474, MDA-231, BT-549 and MCF-7) were incubated with 1-2 nm platinum nanoparticles (0-1000 μg/mL) produced with a cysteine coating. 24 hours later cells were exposed to 2 Gy radiation with a C-arm (Toshiba Infinix VF-i/SP) using 125 KVP to deliver a spectrum of KeV low energy X-rays. After 24 hours the cells were washed and analyzed using a bioluminescence assay to assess cell proliferation based on ATP production. Results: Of the four cell lines tested the BT-474 and BT-549 demonstrated limited reduction in cell proliferation at up to the highest treatment concentration 1000 μg/mL with no radiation exposure. As a result of the limited toxicity of the platinum nanoparticles the effect from increased radiation can be more readily observe when 2 Gy radiation is added resulting a in platinum nanoparticle dose dependent decrease in proliferation in the BT-474 cell line. Nanoparticle Toxicity Concentration of Platinum Nanoparticles (μ/mL) 02505007501000MDA-2311.000±0.0050.995±0.0120.974±0.0130.979±0.0140.777±0.014BT-5491.000±0.0131.003±0.0091.003±0.0170.969±0.0170.894±0.009MCF-71.000±0.0140.960±0.0150.927±0.0220.851±0.0220.769±0.032BT-4741.000±0.0240.961±0.0290.957±0.0330.965±0.0630.985±0.065Table 1: Indexed values for cell proliferation for the BT-474 cell Radiation Toxicity Concentration of Platinum Nanoparticles (μ/mL) 02505007501000*0 Gy1.000±0.0240.961±0.0290.957±0.0330.965±0.0630.985±0.0652 Gy1.027±0.0380.966±0.0230.908±0.0340.870±0.0310.799±0.037Table 2: Indexed values for cell proliferation for the BT-474 cell line 0 and 2 Gy radiation doses, 6 averages. * Student T-TEST P<0.05 Conclusions: At moderate doses of low energy radiation, a reduction in cell proliferation can be detected. This data supports follow-up experiments to add a targeting protein to facilitate uptake by cancer cells based on cell receptor expression. Experiments are current being done to utilize the HER2+ cell receptor upregulation to increase internalization of the particles to achieve a greater effect. Citation Format: Wagner S, Yue Y, Cui X, Zhang G, Bingchen H, Li D, Medina-Kauwe L. Radiation enhancement with cysteine coated platinum nanoparticles. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-12-13.