Modulating trastuzumab density and magnetic targeting duration of pH-sensitive magnetic nanocarriers for synergistically targeting to HER2-positive breast cancer

Abstract

Event Abstract Back to Event Modulating trastuzumab density and magnetic targeting duration of pH-sensitive magnetic nanocarriers for synergistically targeting to HER2-positive breast cancer San-Yuan Chen1* and Chih-Sheng Chiang1* 1 National Chiao Tung University, Department of Materials Science and Engineering, Taiwan To enhance the efficacy of cancer therapy using dual–targeting nanomedicine, we developed a magnetic nanocarrier with controllable Trastuzumab (Tra) density to investigate the therapeutic efficacy via tunable synergistic targeting strategy. Figure 1 depicts the synthesis and the dual–targeting behavior of Tra–functionalized, Dox–encapsulated magnetic nanocarriers (T–Dox–MNCs) through a simple double emulsion process using thiolated PVA/PMAA (PVA/PMASH) and SPIOs, which provide bridging sites for adjusting Tra conjugation and magnetic targeting, respectively. A synergistic dual–targeting strategy combining varied Tra with controllable MT (single vs. multiple) application and different DMAs can significantly alter the accumulation and distribution of MNCs in a tumor. The thiol groups of the PVA/PMASH can be directly exposed in the outer shell to providing different precise conjugation of Tra for HER2 targeting.The Tra–conjugated, Doxorubicin (Dox)–encapsulated magnetic nanocarriers (T–Dox–MNCs) synthesized using thiol–functionalized poly (methacrylic acid)–grafted poly (vinyl alcohol) copolymer (PVA/PMASH) and superparamagnetic nanoparticles can provide bridging sites for adjusting Tra conjugation and display pH-responsive acceleration of Dox release in tumor microenvironment (pH= 5). Results demonstrated that synergistic targeting of modulating physical magnetic field and chemical Tra ligand significantly enhanced the MNCs accumulation and corresponding drug utilization in tumor. More importantly, a new therapeutic strategy of combining multiple short–duration magnetic targeting (MT) and optimal Tra density was for the first time proposed to modulate MNCs biodistribution and blood Dox concentration, which in turn enhances MNC localization in tumors and reduces deposition at the liver and spleen, leading to an 8–fold reduction in tumor volume compared to the control. This study demonstrates that the dual–targeting MNCs provide a feasible nanomedicine platform for achieving excellent therapeutic efficacy for cancer therapy, especially for HER2-positive breast cancers. Keywords: Drug delivery, nanoparticle, theranostic, stimuli-response Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials for therapeutic delivery Citation: Chen S and Chiang C (2016). Modulating trastuzumab density and magnetic targeting duration of pH-sensitive magnetic nanocarriers for synergistically targeting to HER2-positive breast cancer. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02040 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. * Correspondence: Dr. San-Yuan Chen, National Chiao Tung University, Department of Materials Science and Engineering, Hsinchu, Taiwan, Email1 Dr. Chih-Sheng Chiang, National Chiao Tung University, Department of Materials Science and Engineering, Hsinchu, Taiwan, brian4082002@yahoo.com.tw 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 San-Yuan Chen Chih-Sheng Chiang Google San-Yuan Chen Chih-Sheng Chiang Google Scholar San-Yuan Chen Chih-Sheng Chiang PubMed San-Yuan Chen Chih-Sheng Chiang 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.