Event Abstract Back to Event Targeted nanoparticle delivery of a highly toxic metal chelator to brain tumors You Jung Kang1, Achuthammangalam Madhankumar2, James Connor2 and Sheereen Majd3 1 Pennsylvania State University, Biomedical Engineering, United States 2 Pennsylvania State University, Department of Neurosurgery, United States 3 University of Houston, Biomedical Engineering, United States Malignant cells are known to have higher iron requirements compared to healthy cells presumably due to their higher proliferation rate. Therefore, the use of metal chelators has become a promising approach to sensitize and eliminate various cancer cells by depriving these cells from iron. Among the recently developed metal chelators, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), has shown great antiproliferative properties in a number of cancers including lung, melanoma, and neuroepithelioma. However, given the low solubility and high cytotoxicity (IC50 ≈ 30 ± 10 nM) of this metal chelator, its application in treatment of some cancers including deadly brain gliomas requires targeted delivery of this compound. Moreover, the presence of a unique and restrictive barrier between the blood and brain tissue, referred to as the blood-brain barrier (BBB), would limit the entrance of most Dp44mT to the brain reducing its effectiveness during brain cancer treatment. Here, we propose to employ poly(lactic-coglycolide)-b-poly(ethylene glycol) (PLGA-PEG) nanoparticles (NPs) conjugated with Interleukin-13 (IL13) to efficiently encapsulate Dp44mT for targeted delivery of this agent to brain tumor through the BBB. We prepared IL13 conjugated PLGA nanoparticles encapsulating Dp44mT (NP-PEG-IL13) by a modified nanoprecipitation technique. We evaluated the size and shape of NP-Dp44mT using dynamic light scattering (DLS) and scanning electron microscopy (SEM) and demonstrated that these particles were relatively homogenous in size (73.6 ± 11.2 nm) and shape (Figure 1A and B). The obtained NPs also exhibited a good stability without aggregation in physiological solution over a week. Finally, the obtained NP-PEG-IL13 showed a good and controllable release profile. Next, we tested the effect of NP-PEG-IL13 on the cells. These experiments revealed that the uptake rate in glioma cell line, U251, and transcytosis through BBB of NP-PEG-IL13 were significantly higher than NP without IL13 conjugation. Moreover, the cytotoxicity of NP-PEG-IL13 containing Dp44mT was higher than NPs without targeting in U251 cells presumably due to the higher uptake rate. More importantly, NP-PEG-IL13 did not induce significant cell death in healthy endothelial cell line, BBMVEC, indicating a safe and effective strategy for selectively killing malignant cells. In summary, we present a promising approach to selectively deliver a highly toxic metal chelator, Dp44mT, to brain tumors. Our results show that PLGA particles can efficiently encapsulate Dp44mT without affecting its activity, and exhibit an improved solubility and a good stability in physiological solutions. Moreover, the proposed targeted nanocarrier was able to improve the transport across in vitro BBB model, enhance cellular uptake rate, and kill the cancer cells efficiently while sparing normal endothelial cells. Overall, the proposed formula may offer an attractive strategy for effective treatment of malignant brain tumors. Keywords: Drug delivery, targeting delivery, Nano/micro particle Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: General Session Oral Topic: Biomaterials for therapeutic delivery Citation: Kang Y, Madhankumar A, Connor J and Majd S (2016). Targeted nanoparticle delivery of a highly toxic metal chelator to brain tumors. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00297 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers You Jung Kang Achuthammangalam Madhankumar James Connor Sheereen Majd Google You Jung Kang Achuthammangalam Madhankumar James Connor Sheereen Majd Google Scholar You Jung Kang Achuthammangalam Madhankumar James Connor Sheereen Majd PubMed You Jung Kang Achuthammangalam Madhankumar James Connor Sheereen Majd Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.