Acid-sensitive poly(β-cyclodextrin)-based multifunctional supramolecular gene vector. Issue 4 (2nd January 2018)

• Record Type: Journal Article
• Authors: Zhang, Yunti; Jiang, Qimin; Wojnilowicz, Marcin; Pan, Shuaijun; Ju, Yi; Zhang, Wenjie; Liu, Jia; Zhuo, Renxi; Jiang, Xulin
• Is Part Of: Polymer chemistry. Volume 9:Issue 4(2018)
• Page Start: 450
• Page End: 462
• Publication Date: 2018-01-02
• Subjects: Polymers -- Periodicals; Macromolecules -- Periodicals; Polymerization -- Periodicals; 547.705
• DOI: 10.1039/c7py01847a
• Languages: English
• ISSNs: 1759-9954

Abstract

Abstract : Multifunctional host–guest supramolecular PCD-acetal-PGEA/Ad-PEG-FA polyplexes showing FA-targeting and acid-triggered intracellular gene release resulted in good transfection efficiency and low cytotoxicity. Abstract : It is a great challenge to fabricate a gene carrier system containing multiple functional components to overcome the multiple bio-barriers during the gene delivery process. In this work, we developed a supramolecular approach to construct a versatile gene delivery system using two modules with specific functions. Through atom transfer radical polymerization (ATRP) and ring-opening reaction, we synthesized pH-sensitive and brush-shaped ethanolamine functionalized poly(glycidyl methacrylate) (PGEA) derivatives (PCD-acetal-PGEA) as a cationic host module, which contains poly(β-cyclodextrin) as the backbone and acetal bond-linked PGEA as the arms. The cationic host PCD-acetal-PGEA polymer could effectively compact DNA into stable nanosized polyplexes in the extracellular neutral environment and quickly release the DNA in the intracellular acidic environment, which showed lower cytotoxicity and higher transfection efficiency than the PEI control. After the conjugation of the guest module adamantyl terminated polyethylene glycol (Ad-PEG-OH) and adamantyl and folate terminated PEG (Ad-PEG-FA) by host–guest interaction, this multifunctional gene delivery system showed increased serum stability and cell-targeting capacity. In vitro experiments revealed that the uptake efficiency, plasmid DNA transfection efficiency and siRNA silencing efficiency of the FA-targeted supramolecular polyplexes in folate-receptor positive cells were better than those of the control 25 kDa PEI based polyplexes. Therefore, this acid-sensitive multifunctional supramolecular gene vector based on poly(β-cyclodextrin) might be very useful in practical applications.