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Chitosan/siRNA complex in mimetic high-density lipoproteins as specific/hybrid transfection technology for SR-B1 expressing cancer cells
- Source :
- Journal of Drug Delivery Science and Technology; November 2024, Vol. 101 Issue: 1
- Publication Year :
- 2024
-
Abstract
- The development of nanotechnology-based siRNA-delivery systems offers an avenue to improve gene therapy and combined therapies. The radiopharmaceutical 225Ac-DOTA-Bombesin is internalized in cells with high expression of gastrin release peptide receptor (GRPR), such as breast cancer cells (T47D). α-radiation emitted by 225Ac is lethal to the cell due to a high rate of induced double-strand breaks (DSBs). siRNA-RAD51 inhibits RAD51 protein synthesis, preventing the repair of DSBs in DNA. If gene silencing of RAD51 and 225Ac converge in T47D cells, a combined gene/radiation therapy is achieved, since RAD51 silencing by siRNA-RAD51 will prevent cellular repair of 225Ac-induced DSBs. However, siRNA requires an efficient delivery system. In this work, a hybrid technology based on mimetic high-density lipoprotein (mHDL) was developed for siRNA-RAD51 transport. Chitosan/siRNA (CS/siRNA) complexes were prepared and were coated with lipids and Apo-A1 mimetic peptide (D-4F), to assemble mHDL(CS/siRNA). The presence of D-4F peptide targeted the nanosystem to scavenger receptor B1 (SR-B1), which is overexpressed in cancer cells (e.g., T47D cancer cell line). A CS/siRNA-Cy3 complex, with similar chemical properties to CS/siRNA-RAD51, was used for chemical characterization and evaluation of in vitrotransfection. The results showed that mHDL(CS/siRNA-Cy3) is stable in serum, protects siRNA from RNases, and transfects by specific recognition of SR-B1. Pretreatment with mHDL(CS/siRNA-RAD51) resulted in gene silencing and, in combination with 225Ac-DOTA-Bombesin, significantly reduced the viability of T47D cells. The mHDL(CS/siRNA-RAD51) nanosystem is suitable for siRNA-specific transfection, being an efficient and specific/hybrid technology to sensitize cancer cells overexpressing SR-B1.
Details
- Language :
- English
- ISSN :
- 17732247
- Volume :
- 101
- Issue :
- 1
- Database :
- Supplemental Index
- Journal :
- Journal of Drug Delivery Science and Technology
- Publication Type :
- Periodical
- Accession number :
- ejs67672805
- Full Text :
- https://doi.org/10.1016/j.jddst.2024.106274