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- Title
ROS-sensitive selenium-containing cationic brush polymer with potent gene transfection efficiency and biocompatibility.
- Authors
Yonghua Zhai; Lili Wu; Jie Gao; Jingsheng Zhou; Longhai Du; Xiaoda Fu; Yang Gao; Tinglin Zhang; Mengya Zhang; Weihong Lu; Yan Wu
- Abstract
Smart gene delivery vectors are gaining increasing attention in gene therapy, owing to their low cytotoxicity and intrinsic responsiveness. Our previously fabricated novel cationic brush polymer, comprising C Se bonds and tertiary amine EGIn-g-PDMAEMA, shows potential for gene transfection. In this study, its high efficiency for siRNA/pDNA transfection and low cytotoxicity in reactive oxygen species (ROS)-rich microenvironments is substantiated in vitro. Its superior binding capacity with siRNA/pDNA is confirmed by agarose gel electrophoresis assay. The threshold weight ratios for siRNA/pDNA migration delay are 15 and 3 (polymer-to-nucleic acid, w/w), respectively. Fluorescence microscopy and ribonucleotide reductase regulatory subunit M2 gene silencing essay verify the biodegradability and responsive control release of nucleic acids under hydrogen peroxide stimulation in Huh-7 cells. Compared with the gold standard, polyethylenimine 25 kDa, the target polymer displays superior transfection efficiency in ROS-rich tumor cells under serumfree conditions. Furthermore, the vector-nucleic acid complexes exhibit over 90% cell viability at a high concentration of 12 µg mL-1 and good colloidal stability in phosphate-buffered saline (PBS) and 10% fetal bovine serum-PBS for 24 h. The efficient control release and expression of nucleic acids in ROS environments and reduced cytotoxicity highlight the superiority of EGIn-g- PDMAEMA as a gene delivery platform for tumor gene therapy.
- Subjects
GENE transfection; RIBONUCLEOSIDE diphosphate reductase; NUCLEIC acids; GENE expression; CATIONIC polymers; CYTOTOXINS; BIOCOMPATIBILITY; TUMOR suppressor genes; GENETIC vectors
- Publication
Journal of Applied Polymer Science, 2024, Vol 141, Issue 14, p1
- ISSN
0021-8995
- Publication type
Article
- DOI
10.1002/app.55199