Albumin-Based Nanocarriers for the Simultaneous Delivery of Antioxidant Gene and Phytochemical to Combat Oxidative Stress

Saba Naqvi; Vitaly A Khanadeev; Boris N Khlebtsov; Nikolai G Khlebtsov; Monika S Deore; Gopinath Packirisamy

doi:10.3389/fcell.2022.846175

Albumin-Based Nanocarriers for the Simultaneous Delivery of Antioxidant Gene and Phytochemical to Combat Oxidative Stress

Front Cell Dev Biol. 2022 Aug 12:10:846175. doi: 10.3389/fcell.2022.846175. eCollection 2022.

Authors

Saba Naqvi^{1

2}, Vitaly A Khanadeev^{3

4}, Boris N Khlebtsov³, Nikolai G Khlebtsov^{3

5}, Monika S Deore¹, Gopinath Packirisamy^{2

6}

Affiliations

¹ Department of Regulatory Toxicology/Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli, India.
² Nanobiotechnology Laboratory, Department of Biosciences and Bioengineering, Joint Faculty in Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, India.
³ Institute of Biochemistry and Physiology of Plants and Microorganisms, Russian Academy of Sciences, Saratov, Russia.
⁴ Saratov State Agrarian University, Saratov, Russia.
⁵ Saratov State University, Saratov, Russia.
⁶ Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, India.

Abstract

Human serum albumin (HSA) nanoparticles are promising biocompatible, nontoxic, and non-immunogenic platforms for biomedical applications such as bioimaging and drug and gene delivery. The development of nonviral gene delivery vectors is a great challenge for efficient and safe gene therapy. Sulforaphane (SF) can stimulate the expression of antioxidant genes via activation of a nuclear transcription factor, the erythroid-2 related factor 2 (Nrf-2). Here, we use polyethyleneimine (PEI)-stabilized HSA nanoparticles to stimulate endogenous antioxidant defense mechanisms in lung epithelial cells L-132 through the 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 entry of the SOD1 gene and SF-loaded NCs at a very low (3 μg) dose in L-132 cells. A high transfection efficiency of L-132 cells (∼66%, fluorescent microscopy) was obtained with the GFP-tagged transgene SOD1-GFP. We speculate that the antioxidant activity of HSA-PEI-SF-pSOD1 NCs in L-132 cells is due to the initial release of SF followed by subsequent SOD1 gene expression after three to four days of incubation. Hence, the developed HSA-based NCs can be efficient biocompatible nanocarriers for safe and effective drug and gene delivery applications to treat diseases with high oxidative stress due to combinatorial SF and SOD1 gene mechanisms.

Keywords: L-132 cells; antioxidant activity; human serum albumin (HSA); pSOD1 plasmid; sulforaphane.