Symbiotic Self-Assembly Strategy toward Lipid-Encased Cross-Linked Polymer Nanoparticles for Efficient Gene SilencingClick to copy article linkArticle link copied!
- Kingshuk DuttaKingshuk DuttaDepartment of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, United StatesMore by Kingshuk Dutta
- Davide BochicchioDavide BochicchioDepartment of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland, CH-6928 Manno, SwitzerlandMore by Davide Bochicchio
- Alexander E. RibbeAlexander E. RibbeDepartment of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003, United StatesMore by Alexander E. Ribbe
- Dominique AlfandariDominique AlfandariDepartment of Veterinary and Animal Sciences, Molecular and Cellular Biology Program and The Center for Bioactive Delivery- Institute for Applied Life Sciences, University of Massachusetts, Amherst, Massachusetts 01003, United StatesMore by Dominique Alfandari
- Jesse MagerJesse MagerDepartment of Veterinary and Animal Sciences, Molecular and Cellular Biology Program and The Center for Bioactive Delivery- Institute for Applied Life Sciences, University of Massachusetts, Amherst, Massachusetts 01003, United StatesMore by Jesse Mager
- Giovanni M. PavanGiovanni M. PavanDepartment of Innovative Technologies, University of Applied Sciences and Arts of Southern Switzerland, CH-6928 Manno, SwitzerlandDepartment of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, ItalyMore by Giovanni M. Pavan
- S. Thayumanavan*S. Thayumanavan*E-mail: [email protected]Department of Chemistry, Molecular and Cellular Biology Program and The Center for Bioactive Delivery- Institute for Applied Life Sciences, University of Massachusetts, Amherst, Massachusetts 01003, United StatesMore by S. Thayumanavan
Abstract
A novel “symbiotic self-assembly” strategy that integrates the advantages of biocompatible lipids with a structurally robust polymer to efficiently encapsulate and deliver siRNAs is reported. The assembly process is considered to be symbiotic because none of the assembling components are capable of self-assembly but can form well-defined nanostructures in the presence of others. The conditions of the self-assembly process are simple but have been chosen such that it offers the ability to arrive at a system that is noncationic for mitigating carrier-based cytotoxicity, efficiently encapsulate siRNA to minimize cargo loss, be effectively camouflaged to protect the siRNA from nuclease degradation, and efficiently escape the endosome to cause gene knockdown. The lipid–siRNA–polymer (L-siP) nanoassembly formation and its disassembly in the presence of an intracellular trigger have been extensively characterized experimentally and through computational modeling. The complexes have been evaluated for the delivery of four different siRNA molecules in six different cell lines, where an efficient gene knockdown is demonstrated. The reported generalized strategy has the potential to make an impact on the development of a safe and effective delivery agent for RNAi-mediated gene therapy that holds the promise of targeting several hard-to-cure diseases.
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