Anticancer Drug Delivery Using Bioreducible Chitosan for Cancer Therapy
Frontiers in bioengineering and biotechnology(2016)
Abstract
Event Abstract Back to Event Anticancer drug delivery using bioreducible chitosan for cancer therapy Changyong Choi1, Tae-Hun Kim1 and Jae-Woon Nah1 1 Sunchon National University, Department of Polymer Science and Engineering, Korea Introduction: Chemotherapy is one of the most therapies employed in oncology[1]. The development of chemotherapeutic agents for the treatment of cancer has resulted in overcoming some tumors. Despite advances in the synthesis of new anti-tumor agents, these compounds possess inevitable, serious side effects like non-specific toxicity that limit the dose and uses of the drug. To overcome such issues, drug delivery systems (DDSs) such as liposomes, polymeric micelle, and polymeric drug have been studied. DDSs, drug delivery for cancer therapy, are rapidly progressing and are being implemented to overcome the limitations of conventional chemotherapeutic agents which are nonspecific biodistribution in the body, poor water solubility and low therapeutic indices[2]. The high metabolic rate of tumor tissues often leads to acidosis (pH < 7), and ATP-mediated proton accumulation makes endosomal and lysosomal compartments of cells significantly more acidic (pH 5.0-6.2) than the cytosol or intracellular space. The acidic environment of tumors has been utilized to trigger the disassembly of delivery systems. Therefore, pH-responsive nanocarriers systems offer several important benefits for cancer therapy[1]. In addition, investigators are exploring the possibility of integrating active targeting ligands in pH-responsive nanocarriers systems for targeted cancer chemotherapy. In this study doxorubicin (DOX)-conjugated chitosan (CHD) was synthesized by hydrazone bond. The hydrazone bond is hydrolysis in acidic pH (pH 5.0). In addition, the synthesized CHD was conjugated transferrin (TCHD) for targeting of transferrin receptor overexpressed cancer cell. Experimental Methods: Conjugation of doxorubicin (DOX) to chitosan (CHD) was accomplished by formation of hydrazone between the ketone of DOX and the hydrazide of chitosan. Transferrin was prepared transferrin-PEG conjugate (TP) form for modification of CHD. The TP-CHD (TCHD) conjugate was reacted by coupling reaction. The characterization of TCHD was investigated by 1H-NMR, and dynamic light scattering (DLS). The DOX release property from CHD was investigated according to the various pH conditions by HPLC. Evaluation of in vitro cell cytotoxicity (against to L929) and antitumor activity (against to KB, LoVo, etc.) were confirmed by MTT. Results and Discussion: TCHD prepared in our study not only inhibit proliferation of tumor cell but also reduce toxicity in the normal cell due to specific target. The chemical structure of CHD was investigated by 1H-NMR. In addition, DOX release profiles of the CHD were accomplished in pH 5.0 and 7.4 condition. This pH-dependent DOX release behaviour is highly desirable for targeted cancer therapy because it could significantly minimize the amount of premature drug release during circulation in the bloodstream (pH 7.4), but provided the possibility of burst drug release once the CHD was internalized through endocytic pathway and enter the acidic late endosome (pH 5.0). The cell cytotoxicity and antitumor activity of the CHD and TCHD were confirmed by MTT assay. The cancer cell was treated with various formulations of CHD and TCHD at concentrations ranging from 0.00015–0.005 ㎍/mL. In the cancer cell IC50 was 0.002 ㎍/mL. In comparison, antitumor activity of the CHD was higher than TCHD. This result demonstrated that TCHD was specific cellular uptake by receptor mediated endocytosis facilitated by the transferrin ligand of TCHD and the trnaferrin receptor present on the surface of the cancer cell. Conclusion: In this study, we synthesized targeting ligand-modified pH-sensitive polymeric drug. The antitumor activity of TCHD was demonstrated against transferrin receptor overexpressed cell by MTT assay. The IC50 of TCHD was confirmed 0.002 ㎍/mL in cancer cell. The antitumor activity considered that TCHD might be increased antitumor activity by receptor-mediated endocytosis. The result suggested that TCHD might be a promised anticancer drug carrier for cancer therapy. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning. (No. NRF-2014R1A2A1A10053027).References:[1] Chunxi. L., Fengxi. L., Lixia. F., Min. L., Jian. and Z., Na. Z., 2013. Biomaterials. 34: 2547-2564.[2] Shuabg. C., Sharadvi. T., Taryn. R. B., Hassam. D., Neal. M, D., Mark. S. C., and Laird. F., 2010. J. Control. Release. 146: 212-218. Keywords: Drug delivery, biomaterial, nanoparticle, Polymeric material Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials for therapeutic delivery Citation: Choi C, Kim T and Nah J (2016). Anticancer drug delivery using bioreducible chitosan for cancer therapy. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02392 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 Changyong Choi Tae-Hun Kim Jae-Woon Nah Google Changyong Choi Tae-Hun Kim Jae-Woon Nah Google Scholar Changyong Choi Tae-Hun Kim Jae-Woon Nah PubMed Changyong Choi Tae-Hun Kim Jae-Woon Nah Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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