Abstract
Endo/lysosomal escape and subsequent nuclear translocation are recognized as the two major challenges for efficient gene transfection. Herein, nuclear localization signal (NLS) peptide sequences and oligomeric lysine sequences were crosslinked via disulfide bonds to obtain glutathione (GSH) reducible polypeptide (pNLS). The pNLS could condense DNA into compact positive-charged complexes with redox sensitivity, and then gold nanoclusters (AuNC) were further decorated to the surface via electrostatic interactions obtaining versatile pNLS/DNA/AuNC complexes. The AuNC could generate reactive oxygen species (ROS) under NIR-irradiation and accelerate the endo/lysosomal escape of the complexes, and then the pNLS sequence degraded by GSH in cytoplasm would release the DNA and facilitate the subsequent nuclear translocation for enhanced gene transfection.
Highlights
Gene therapy is considered as a promising treatment for many serious diseases, including cancer, and mainly restricted by the success of gene delivery [1,2]
The morphologies of free AuNC in deionized water, pNLS/DNA complexes at w/w ratio of 50:1 and pNLS/DNA/AuNC complexes at w/w/w ratio of 50:1:5 in 10 mM phosphate buffered saline (PBS) were observed by transmission electron microscopy (TEM, JEM-2100, JEOL Ltd., Tokyo, Japan)
Irradiation intensity and period, the obtained pNLS/DNA/AuNC complexes would only destroy the acidic organelles without evoking proliferation inhibition of the irradiated cells
Summary
Gene therapy is considered as a promising treatment for many serious diseases, including cancer, and mainly restricted by the success of gene delivery [1,2]. Cell penetration peptide (CPP) and nuclear localization sequence (NLS) were vastly used in non-viral gene carrier decoration [9,10] Ascribed to their electropositive structure, CPPs and NLSs were cross-linked by sensitive linkers to form intracellular environment-responsive polypeptides with enhanced gene delivery capacity [11]. Liu et al reported a light-responsive gene carrier for concurrently endo/lysosomal escape and gene generating reactive oxygen species (ROS) [24]. Introduced into RSP for endo/lysosome escape enhancement, since the AuNC holds the merits of electropositive peptide sequence (CKKKKKKC) and nuclear location sequence NLS (CPKKKRKVC). Were cross-linked by disulfide bond to a obtain RSP (pNLS) with both gene compact and nucleus electropositive peptide sequence (CKKKKKKC) and nuclear location sequence NLS (CPKKKRKVC). Facile construction of the NIR light-responsive and redox-sensitive pNLS/DNA/AuNC complexes for photo‐triggered endo/lysosomal escape and gene delivery. Complexes for photo-triggered endo/lysosomal escape and gene delivery
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