Investigation of drug/microRNA co-delivery system for simultaneously inhibiting both common cancer cells and cancer stem cells

Event Abstract Back to Event Investigation of drug/microRNA co-delivery system for simultaneously inhibiting both common cancer cells and cancer stem cells Yong Sun1, Yani Cui1, Junhui Sui1, Yujiang Fan1 and Xingdong Zhang1 1 National Engineering Research Center for Biomaterials, Sichuan University, China In the past decades, polymeric nano-drug delivery system has made great progress in the treatment of malignant tumor. However, the tumor faces recurrence and metastasis when stopping target drug or gene therapy, resulting in more serious complications. Recent study revealed that this phenomenon lies in the existence of a small group of specific cells in the cancer cells, called “cancer stem cells”, which are highly tolerant of normal chemotherapy and genetherapy.Although specific microRNA can effectively inhibit the growth of cancer stem cells and metastasis. The solo treatment of cancer stem cells can't effective inhibit the proliferation of tumor, because there were a large number of common cancer cells existing in tumor tissues, and mature common cancer cells possibly mutated into cancer stem cells. This project plans to design a kind of reduction sensitivite cationic polymeric micelles. In the hydrophilic cationic outer shell, the micelles complex microRNAs via electrostatic interaction which can inhibit the growth and metastasis of cancer stem cells and promote cancer stem cells differentiation into common cancer cells; Meanwhile, in the hydrophobicity inner core, the micelles load adriamycin with efficient anti-proliferation effect to common tumor cells, in order to achieve the purpose of inhibiting both common cancer cells and cancer stem cells simultaneously, and enhancing anti-tumor therapeutic effect, preventing recurrence and metastasis of tumor. The results indicated the cationic polymeric micelles could stablily encapsulate the DOX, and complex microRNAs on the surfaces of micelles via electrostatic interaction. The nano-size of the both empty micelles and DOX-encapsulated micelles was range from 50 nm to 200 nm while narrow size distribution. The cytotoxicity experiments demonstrated that the PAA-g-PEG/PArg micelles have good biocompatibility as same as control sample, compared with Dox-incorporated PAA-g-PEG/PArg micelle group, the co-delivery of drug and gene PAA-g-PEG/PArg micelles groups were more efficiently internalized into MCF-7 cells, and enhance the ability of inhibitting cell proliferation by CLSM and flow cytometry test. In the MCF-7-bearing nude mouse models, the PAA-g-PEG/PArg micelles groups could efficiently accumulate in the tumor site by the fluorescence optical imaging technique, meanwhile, it demonstrated excellent solid tumor growth inhibition effect and the capacity for preventing recurrence and metastasis of tumor by investigating the tumor volume and body weight changes, as well as survive study of the tumor-bearing Balb/c mice. The PAA-g-PEG/PArg cationic polymeric micelles as a safe and high efficiency drug delivery system was expected to be a promising co-delivery carrier system that enables simultaneously targeting delivery hydrophobic chemotherapy drugs and negative charge of therapeutic siRNA molecules to tumor tissue and significantly enhanced antitumor effects. National Natural Science Foundation of China (Grant No. 21174090, 51403138) and Young Teachers Science Foundation of Sichuan University (Grant No. 2014SCU11016).References:[1] Du L, Wang H, He L, Zhang J, Ni B, Wang X, Jin H, Cahuzac N, Mehrpour M, Lu Y: CD44 is of functional importance for colorectal cancer stem cells. Clinical Cancer Research 2008, 14(21):6751-6760.[2] Prince M, Sivanandan R, Kaczorowski A, Wolf G, Kaplan M, Dalerba P, Weissman I, Clarke M, Ailles L: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proceedings of the National Academy of Sciences 2007, 104(3):973-978.[3] Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nature medicine 2011, 17(2):211-215. Keywords: Gene Therapy, stem cell, Drug delivery, Biodegradable material Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials for therapeutic delivery Citation: Sun Y, Cui Y, Sui J, Fan Y and Zhang X (2016). Investigation of drug/microRNA co-delivery system for simultaneously inhibiting both common cancer cells and cancer stem cells. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02803 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 Yong Sun Yani Cui Junhui Sui Yujiang Fan Xingdong Zhang Google Yong Sun Yani Cui Junhui Sui Yujiang Fan Xingdong Zhang Google Scholar Yong Sun Yani Cui Junhui Sui Yujiang Fan Xingdong Zhang PubMed Yong Sun Yani Cui Junhui Sui Yujiang Fan Xingdong Zhang Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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