Dopamine-mimetic-coated polyamidoamine-functionalized Fe<sub>3</sub>O<sub>4</sub> nanoparticles for safe and efficient gene delivery

doi:10.1007/s11706-023-0637-9

Front. Mater. Sci.

2023, Vol. 17

Issue (1) : 230637 https://doi.org/10.1007/s11706-023-0637-9

RESEARCH ARTICLE

Dopamine-mimetic-coated polyamidoamine-functionalized Fe₃O₄ nanoparticles for safe and efficient gene delivery

Liang Liu¹(

), Chaobing Liu¹, Zhaojun Yang¹, Yiran Chen¹, Xin Chen¹, Jintao Guan²

¹. College of Life Science and Technology, Wuhan Polytechnic University, Wuhan 430023, China
². College of Chemistry and Environmental Engineering, Wuhan Polytechnic University, Wuhan 430023, China

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Abstract

Fe₃O₄ nanoparticles (NPs) are widely used in the construction of drug and gene delivery vectors because of their particular physicochemical properties. Surface modification can not only reduce the cytotoxicity of Fe₃O₄, but also further improve the biocompatibility and delivery efficiency. In this work, firstly, polydopamine (PDA)-coated Fe₃O₄ NPs (named Fe₃O₄@PDA) were prepared by using the self-polymerization characteristics of dopamine in alkaline environment. Then, polyamidoamine (PAMAM) was modified by the Michael addition reaction to prepare water-soluble core‒shell magnetic NPs of Fe₃O₄@PDA@PAMAM, and its potential as gene vector was further evaluated. The results revealed that Fe₃O₄@PDA@PAMAM had the ability to condense and protect DNA, and showed lower cytotoxicity, higher cell uptake and transfection efficiency than those of PAMAM. It has the potential to become a magnetic targeted gene vector for further study.

Keywords gene vector nanoparticle polydopamine gene transfection

Corresponding Author(s): Liang Liu

About author:

Changjian Wang and Zhiying Yang contributed equally to this work.

Issue Date: 06 March 2023

Cite this article:

Liang Liu,Chaobing Liu,Zhaojun Yang, et al. Dopamine-mimetic-coated polyamidoamine-functionalized Fe₃O₄ nanoparticles for safe and efficient gene delivery[J]. Front. Mater. Sci., 2023, 17(1): 230637.

URL:

https://academic.hep.com.cn/foms/EN/10.1007/s11706-023-0637-9
https://academic.hep.com.cn/foms/EN/Y2023/V17/I1/230637

Scheme1 Schematic preparation of Fe₃O₄@PDA@PAMAM NPs.

Fig.1 (a) FTIR spectra, (b) TGA curves, (c) XRD patterns, (d) magnetic hysteresis loops, and (e) DLS results of Fe₃O₄, Fe₃O₄@PDA, and Fe₃O₄@PDA@PAMAM NPs. (f) Zeta potentials of PAMAM/ctDNA polyplexes and Fe₃O₄@PDA@PAMAM/ctDNA polyplexes. (g)(h)(i) TEM images of Fe₃O₄, Fe₃O₄@PDA, and Fe₃O₄@PDA@PAMAM NPs (from left to right). Mean ± SD, n = 3, *P < 0.05, and **P < 0.01.

Fig.2 Cytotoxicity and RTCA results: concentration-dependent growth inhibition of (a) HepG2, (b) HeLa, and (c) HEK-293T cells by Fe₃O₄@PDA@PAMAM NPs and PAMAM (cell viability was determined using the MTT assay and results are expressed as mean ± SD in triplicate); concentration-dependent growth curves of (d) HepG2, (e) HeLa, and (f) HEK-293T cells by Fe₃O₄@PDA@PAMAM NPs. Mean ± SD, n = 3, *P < 0.05, and **P < 0.01.

Fig.3 DNA binding and protection ability of Fe₃O₄@PDA@PAMAM: (a) DNA condensation ability in PBS; (b) DNA binding ability in serum; (c) DNA protection ability in PBS; (d) DNA protection ability in serum. All samples were run on a 1% agarose gel and stained with EtBr.

Fig.4 The DNA release from Fe₃O₄@PDA@PAMAM/pDNA polyplexes at different pH values.

Fig.5 Cell uptake results of Fe₃O₄@PDA@PAMAM/pDNA and PAMAM/pDNA: (a) fluorescence microscopy images of (40×) intracellular trafficking of the FITC labeled Fe₃O₄@PDA@PAMAM/pDNA and PAMAM/pDNA polyplexes in HEK-293T cells (blue: DAPI-stained cell nuclei; green: Fe₃O₄@PDA@PAMAM and PAMAM; scale bar = 1000 μm); (b)(c) flow cytometry results of the cell uptake efficiency of Fe₃O₄@PDA@PAMAM/pDNA and PAMAM/pDNA polyplexes with various N/P ratios in HEK-293T cells.

Fig.6 Gene transfection results of various Fe₃O₄@PDA@PAMAM/pDNA and PAMAM/pDNA in HEK-293T, HepG2, and HeLa cells: (a) fluorescence microscopy images (40×) of positive GFP expression cells treated with various N/P ratios of Fe₃O₄@PDA@PAMAM/pDNA and PAMAM/pDNA polyplexes (scale bar = 1000 μm); (b)(c)(d) flow cytometry results of the gene transfection in HEK-293T, HepG2, and HeLa cells, respectively. Mean ± SD, n = 3, *P < 0.05, **P < 0.01, and ***P < 0.005.

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