Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

Citation: Udukala, D. N., Wang, H. W., Wendel, S. O., Malalasekera, A. P., Samarakoon, T. N., Yapa, A. S., . . . Bossmann, S. H. (2016). Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection. Beilstein Journal of Nanotechnology, 7, 364-373. doi:10.3762/bjnano.7.33Additional Authors: Ortega, R.;Toledo, Y.;Bossmann, L.;Robinson, C.;Janik, K. E.;Koper, O. B.;Motamedi, M.;Zhu, G. H.Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl) porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis

Incorporating I-131 into a PAMAM (G5.0) dendrimerconjugate: design of a theranostic nanosensor for medullary thyroid carcinoma

Citation: He, R., Wang, H., Su, Y., Chen, C., Xie, L., Chen, L., . . . Bossmann, S. H. (2017). Incorporating I-131 into a PAMAM (G5.0) dendrimerconjugate: design of a theranostic nanosensor for medullary thyroid carcinoma. Rsc Advances, 7(26), 16181-16188. doi:10.1039/c7ra00604gWe report the synthesis and purification of a targeting probe for Medullary Thyroid Carcinoma (MTC) by incorporating I-131 into PAMAM (G5.0) dendrimers. Both the I-131 labeled control dendrimer (I-131-PAMAM (G5.0) without attached targeting peptide) and the MTC-targeting dendrimer (I-131-PAMAM (G5.0) attached to VTP (vascular targeting peptide)) were labeled with the radioisotope I-131 by applying the iodogen method. The resulting G5.0 dendrimers were purified by means of ultracentrifugation. The labelling efficiencies and radiochemical purities vs. time were determined by paper chromatography. The radiolabeling efficiencies of I-131-PAMAM (G5.0) and I-131-PAMAM (G5.0) were 93 +/- 1% and 85 +/- 2%, respectively. I-131-PAMAM (G5.0) did exhibit small, but significant changes in radiochemical purity as a function of time after labelling. The highest observed highest purity was 82 +/- 2%. I-131-PAMAM (G5.0)VTP did display larger changes in radiochemical purity as a function of time after labelling, maximally 80 +/- 2%. The stability of the two probes and their binding behavior to the human medullary thyroid cancer cell line (TT) were observed in vitro. Compared to the negative control group (consisting of (NaI)-I-131), the TT cell binding rate of 131I-PAMAM (G5.0)-VTP was significantly increased at 48 h and 72 h (P 0.05). These findings have been confirmed by performing MTT assays. These results confirm earlier findings, which demonstrated fast uptake of PAMAM (G5.0) by various cell types

Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model

Matthew T Basel1, Sivasai Balivada1, Hongwang Wang2, Tej B Shrestha1, Gwi Moon Seo1, Marla Pyle1, Gayani Abayaweera2, Raj Dani2, Olga B Koper2, Masaaki Tamura1, Viktor Chikan2, Stefan H Bossmann2, Deryl L Troyer11Department of Anatomy and Physiology, College of Veterinary Medicine, 2Department of Chemistry, Kansas State University, Manhattan, KS, USAAbstract: Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer.Keywords: cytotherapy, pancreatic cancer, disseminated peritoneal carcinomatosis, targeted magnetic hyperthermia, nanoparticle