Csaba Noémi

Garcia-Fuentes Marcos

Gutierrez-Gutierrez Sara

English

University of Szeged

VI. Symposium of Young Researchers on Pharmaceutical Technology, Biotechnology and Regulatory Science January 24-26 2024 - Szeged, Hungary  34  OP-15 DOI: 10.14232/syrptbrs.2024.34 Polyphosphazene nanocarriers for RNA delivery Sara Gutierrez-Gutierrez1,2, Noemi Csaba1,2, Marcos Garcia-Fuentes1,2  1CiMUS Research Center, Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Spain 2Institute of health Research of Santiago (IDIS), Santiago de Compostela, Spain  Poly(organo)phosphazenes (PPZs) are new, versatile polymers of great interest as biomaterials for medical applications, and concretely for gene delivery [1]. Previous studies from our group showed that 6-mercaptohexanoic acid alkyl carboxylate-poly(phosphazene) (6MHA-PPZ) can enhance transfection efficiency of gene nanocomplexes (NCs) while reducing their cytotoxicity [2].  Herein, we designed three novel prototypes of NCs and explored their potential for pDNA and cmRNA delivery in vitro glioblastoma models. To achieve this, we synthesized two new cationic PPZs along with the anionic 6MHA-PPZ using a multistage reaction previously reported by our group [2]. The products were characterized by 31P and 1H NMR. Next, NCs were prepared based on the two cationic PPZs, or the commercial reagent polyethyleneimine (PEI), and their combination with 6MHA-PPZ. All formulations presented sizes between 80 and 150 nm and positive surface charge, which are adequate for their use in gene therapy. Additionally, we observed that all formulations could complex the nucleic acids and release them in the presence of an anionic competitor. Finally, NCs loaded with pDNA and cmRNA were tested for toxicity and GFP expression in the GL261 cell line. The three formulations were non-toxic until a median dose of 250 ng/cm2. Data from fluorimetry and flow cytometry studies confirmed the possibility to induce efficient GFP expression with formulations loaded with pDNA and cmRNA. In conclusion, our studies highlight the potential of various PPZ-based materials as versatile components to constitute a new generation of nanocomplexes (NCs) designed for efficient gene delivery in brain cancer.   References: 1. W.H. Hsu, J. Appl. Polym. Sci. 2020, 137, 25, 48688. 2. WH. Hsu, Adv. Ther. 2019, 2(3), 1800126   

Polyphosphazene nanocarriers for RNA delivery : [abstract]

http://acta.bibl.u-szeged.hu/84421/1/syrptbrs_2024_034.pdf

Polyphosphazene nanocarriers for RNA delivery : [abstract]

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