Theranostics 2018; 8(1):1-12. doi:10.7150/thno.21052 This issue Cite

Research Paper

Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation

Zhihang Chen, Balaji Krishnamachary, Marie-France Penet, Zaver M. Bhujwalla

Division of Cancer Imaging Research, Johns Hopkins University School of Medicine, Russell H. Morgan Dept. of Radiology & Radiological Science, Baltimore, MD 21205, USA

Citation:
Chen Z, Krishnamachary B, Penet MF, Bhujwalla ZM. Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation. Theranostics 2018; 8(1):1-12. doi:10.7150/thno.21052. https://www.thno.org/v08p0001.htm
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Abstract

Graphic abstract

Purpose: Effective in vivo delivery of siRNA to silence genes is a highly sought-after goal in the treatment of multiple diseases. Cyclooxygenase-2 (COX-2) is a major mediator of inflammation and its effective and specific downregulation has been of major interest to treat conditions ranging from auto-immune diseases to gastric inflammation and cancer. Here we developed a novel and efficient method to produce a multiple imaging reporter labeled cationic dextran nanopolymer with cleavable positive charge groups for COX-2 siRNA delivery.

Methods: Small molecules containing amine groups were conjugated to the dextran scaffold through acetal bonds that were cleaved in weak acid conditions. With multiple imaging reporters located on different regions of the nanopolymer, cleavage of acetal bonds was visualized and quantified by imaging, for the first time, in cancer cells and tumors.

Results: The biocompatibility of dextran and the rapid cleavage and release of amine groups minimized proinflammatory side effects and COX-2 induction observed with other siRNA carriers, to successfully achieve COX-2 downregulation in cancer cells and tumors. Imaging results confirmed that this nanoplex, consisting of the dextran nanopolymer with COX-2 siRNA, accumulated in tumors, and the amine functional groups were rapidly cleaved in cancer cells and tumors. Along with effective downregulation of COX-2, we also demonstrated, for the first time, effective downregulation of its major product prostaglandin E2 (PGE2).

Conclusions: We successfully developed an efficient method to produce an acid-degradable dextran nanopolymer containing cleavable amine groups as the siRNA carrier. Because of its biocompatibility, this degradable dextran delivered COX-2 siRNA within tumors and efficiently downregulated COX-2 expression.

Keywords: dextran, COX-2 siRNA therapy, biodegradable polymer, imaging, cancer


Citation styles

APA
Chen, Z., Krishnamachary, B., Penet, M.F., Bhujwalla, Z.M. (2018). Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation. Theranostics, 8(1), 1-12. https://doi.org/10.7150/thno.21052.

ACS
Chen, Z.; Krishnamachary, B.; Penet, M.F.; Bhujwalla, Z.M. Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation. Theranostics 2018, 8 (1), 1-12. DOI: 10.7150/thno.21052.

NLM
Chen Z, Krishnamachary B, Penet MF, Bhujwalla ZM. Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation. Theranostics 2018; 8(1):1-12. doi:10.7150/thno.21052. https://www.thno.org/v08p0001.htm

CSE
Chen Z, Krishnamachary B, Penet MF, Bhujwalla ZM. 2018. Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation. Theranostics. 8(1):1-12.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
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