Antioxidant albumin-based nanocomposites containing sulforaphane drug and superoxide dismutase plasmid
Human serum albumin (HSA) nanostructures are promising biocompatible, non-immunogenic and non-toxic platform for biomedical applications such as bioimaging and gene and drug delivery. The development of non-viral gene delivery vectors for safe and efficient gene therapy is a great challenge. Sulforaphane (SF) can stimulate the expression of antioxidant genes via activation of a transcription factor, nuclear factor-erythroid-2–related factor 2 (Nrf2). In this work, we use polyethylenimine (PEI) stabilized HSA nanoparticles to stimulate endogenous antioxidant defense mechanisms in lung epithelial cells L-132 through combinatorial effect of SF drug and antioxidant superoxide dismutase 1 gene (pSOD1 plasmid) delivered by HSA-PEI-SF-pSOD1 nanocomposites (NCs). The developed NCs demonstrated high biocompatibility (L-132 viability, >95%, MTT assay,) and high antioxidant activity because of efficient enter L-132 cells and delivery of encoding SOD1 gene and SF at a very low 3 µg dose. A high transfection efficiency of L-132 cells (~66%, fluorescent microscopy) was obtained with the GFP tagged transgene SOD1-GFP. We suggest that the antioxidant activity of HSA-PEI-SF-pSOD1 NCs in L-132 cells is due to initial release of SF followed by subsequent SOD1 gene expression after three to four days of incubation. Thus, the developed HSA-based NCs can be efficient biocompatible nanocarriers for safe and effective drug and gene delivery applications to treat diseases with the high oxidative stress due to combinatorial SF and SOD1 gene mechanisms.
The work was supported by the DST-International Division (grant: INT/RUS/RFBR/P-235), Government of India and Russian Foundation for Basic Research (grant number: 16-52-45026). SN was supported by Women Scientist Scheme (WOS-A), DST, Government of India, (Grant No. SR/WOS-A/LS-1224/2015). The work by VK was supported by the grant from the President of the Russian Federation (grant number: MK- 1867.2019.2).
Institute of Biochemistry and Physiology of Plants and Microorganisms Russian Academy of Sciences (IBPPM RAS)
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