Conjugation chemistry through acetals toward a dextran-based delivery system for controlled release of siRNA
KAUST DepartmentChemical Science Program
Office of the VP
Physical Science and Engineering (PSE) Division
Online Publication Date2012-09-18
Print Publication Date2012-09-26
Permanent link to this recordhttp://hdl.handle.net/10754/562333
MetadataShow full item record
AbstractNew conjugation chemistry for polysaccharides, exemplified by dextran, was developed to enable the attachment of therapeutic or other functional moieties to the polysaccharide through cleavable acetal linkages. The acid-lability of the acetal groups allows the release of therapeutics under acidic conditions, such as that of the endocytic compartments of cells, regenerating the original free polysaccharide in the end. The physical and chemical behavior of these acetal groups can be adjusted by modifying their stereoelectronic and steric properties, thereby providing materials with tunable degradation and release rates. We have applied this conjugation chemistry in the development of water-soluble siRNA carriers, namely acetal-linked amino-dextrans, with various amine structures attached through either slow- or fast-degrading acetal linker. The carriers with the best combination of amine moieties and structural composition of acetals showed high in vitro transfection efficiency and low cytotoxicity in the delivery of siRNA. © 2012 American Chemical Society.
SponsorsThis work was funded through Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract No. HHSN268201000043C), and the Frechet "various donors" gift fund for the support of research in new materials. P. R. Wich gratefully acknowledges the Alexander von Humboldt Foundation (AvH) for funding. We also thank A. Fischer in the UC Berkeley Cell Culture Facility for her help with cell culture preparation.
PublisherAmerican Chemical Society (ACS)
- Degradation of acetalated dextran can be broadly tuned based on cyclic acetal coverage and molecular weight.
- Authors: Chen N, Collier MA, Gallovic MD, Collins GC, Sanchez CC, Fernandes EQ, Bachelder EM, Ainslie KM
- Issue date: 2016 Oct 15
- Spirocyclic Acetal-Modified Dextran as a Flexible pH-Sensitive Solubility-Switching Material.
- Authors: Graham ET, Broaders KE
- Issue date: 2019 May 13
- Acetal-derivatized dextran: an acid-responsive biodegradable material for therapeutic applications.
- Authors: Bachelder EM, Beaudette TT, Broaders KE, Dashe J, Fréchet JM
- Issue date: 2008 Aug 13
- Acetals as pH-sensitive linkages for drug delivery.
- Authors: Gillies ER, Goodwin AP, Fréchet JM
- Issue date: 2004 Nov-Dec
- Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation.
- Authors: Chen Z, Krishnamachary B, Penet MF, Bhujwalla ZM
- Issue date: 2018