Abstract
In this work, zoledronic acid-loaded cationic methylcellulose polyplex nanoparticles were developed for enhanced gene delivery efficiency and breast cancer cell killing effect. Zoledronic acid (Zol) is one of bisphosphonate derivatives, which is used for osteoporosis treatment and also can induce apoptosis to breast cancer cells. First, cationic methylcellulose (MCPEI) was synthesized by reductive amination of polyethylenimine (PEI, 0.8 kDa) with periodate-oxidized methylcellulose (MC). Negatively charged Zol was introduced to MCPEI polyplexes via surface coating of polyplex (Zol(MCPEI/pDNA)) or loading into polyplexes (MCPEI/(pDNA + Zol)). The complexes with suitable size for efficient transfection could be formed via loading method. MCPEI/(pDNA + Zol) complexes showed higher stability and endosome buffering capacity than MCPEI polyplexes, probably due to imidazole group of Zol. Although the transfection efficiency of Zol(MCPEI/pDNA) complexes was similar with or less than that of MCPEI polyplexes, MCPEI/(pDNA + Zol) complexes showed much higher transfection efficiency than MCPEI polyplexes in HeLa cells. In the bafilomycin A1-treated transfection results, the transfection efficiency of MCPEI/(pDNA + Zol) complexes was significantly decreased. These results mean that the transfection of MCPEI/(pDNA + Zol) complexes would be mediated by endocytosis and loaded Zol could improve the transfection efficiency of MCPEI polyplexes via endosome buffering. In addition, breast cancer cell killing effect of MCPEI/(pDNA + Zol) was examined using pJDK-apoptin in MDA-MB-231 cells. MCPEI/(pJDK-apoptin + Zol) complexes showed the highest cancer cell killing effect due to the combinatorial effect of Zol and apoptin. It is concluded that zoledronic acid-loaded polyplexes could improve the transfection efficiency and MCPEI/(pDNA + Zol) complexes showed the potential for anticancer therapy.
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Acknowledgements
This work was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2017R1D1A1B03030556) and the Korean government (Ministry of Science and ICT) (NRF-2020R1A2C1011669).
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Seo, J., Jeong, S., Lee, M. et al. Zoledronic acid-loaded cationic methylcellulose polyplex nanoparticles for enhanced gene delivery efficiency and breast cancer cell killing effect. Appl Nanosci 12, 3303–3314 (2022). https://doi.org/10.1007/s13204-021-02127-5
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DOI: https://doi.org/10.1007/s13204-021-02127-5