Posted by Gene therapy can be an efficient method to treat genetic diseases, including cancer. However, the lack of biocompatible gene delivery systems with minimal toxicity limits the clinical success of this approach. This paper reports on the synthesis of an effective gene carrier using gold nanostars (AuNSs) in combination with chitosan (CS), β-cyclodextrin (CD), and branched-poly(ethylene imine) (bPEI) as a bionanocomposite (BNC) with minimal toxicity for gene delivery applications. The new gene delivery sytem was characterized the AuNS@CS–CD–bPEI (AuNS@CCP) BNC using various analytical methods.
The applicability of the BNC in nucleic acid transfection was evaluated in various mammalian cell lines (HEK293T, LN308, MDA-MB-231, and CT-26) using firefly luciferase-zetagreen (FLuc-ZsGreen) reporter genes by optical imaging, and synthetic mRNA coding for SARS-CoV-2 spike protein by immunoblot analysis to prove the ability of the BNC to transfect both DNA and RNA. We also characterized the N/P ratio of the BNC with the nucleic acids to optimize cell transfection efficiency. The cytotoxicity study (MTT assay) of the BNC showed no significant toxicity when used at the optimal N/P ratio.
Overall, it is shown that the synthesized BNC has a high potential for use as a gene delivery agent for in vivo applications, potentially using various delivery routes such as intranasal, intramuscular, intrathecal, and intraperitoneal in treating genetic diseases and for vaccines in infectious diseases.
Farbod Tabesh, Golnaz Haghverdi, Kireeti Phani Devarakonda, Tarik F Massoud and Ramasamy Paulmurugan (2024) Synthesis, characterization, and application of a biocompatible gene delivery nanocarrier constructed from gold nanostars and a chitosan–cyclodextrin–poly(ethylene imine) graft polymer. Mater. Adv.. https://doi.org/10.1039/D4MA00433G