Sodium Alginate-Doping Cationic Nanoparticle As Dual Gene Delivery System for Genetically Bimodal Therapy

Abstract

Photodynamic therapy occupies an important position in cancer therapy because of its minimal invasiveness and high spatiotemporal precision, and photodynamic/gene combined therapy is a promising strategy for additive therapeutic effects. However, the asynchronism and heterogeneity between traditional chemical photosensitizers and nucleic acid would restrict the feasibility of this strategy. KillerRed protein, as an endogenous photosensitizer, could be directly expressed and take effect in situ by transfecting KillerRed reporter genes into cells. Herein, a simple and easily prepared sodium alginate (SA)-doping cationic nanoparticle SA@GP/DNA was developed for dual gene delivery. The nanoparticles could be formed through electrostatic interaction among sodium alginate, polycation, and plasmid DNA. The title complex SA@GP/DNA showed good biocompatibility and gene transfection efficiency. Mechanism studies revealed that SA doping could facilitate the cellular uptake and DNA release. Furthermore, SA@GP/DNA was applied to the codelivery of p53 and KillerRed reporter genes for the synergistic effect combining p53-mediated apoptosis therapy and KillerRed-mediated photodynamic therapy. The ROS generation, tumor cell growth inhibition, and apoptosis assays proved that the dual-gene transfection could mediate the better effect compared with single therapy. This rationally designed dual gene codelivery nanoparticle provides an effective and promising platform for genetically bimodal therapy.

ROS-Responsive Bola-Lipid Nanoparticles as a Codelivery System for Gene/Photodynamic Combination Therapy

“…Next, the levels of apoptosis-related proteins, such as caspase-3, caspase-8, and caspase-9, in the cells treated with different treatments were measured. Caspases (cysteinyl aspartate-specific proteases) are a family of proteases that play an important role in apoptosis . Caspase-3 is the most critical apoptosis-executing protease in the process of apoptosis and can be activated by caspase-8 and caspase-9, which are related to the death receptor apoptosis pathway and mitochondria-dependent apoptosis pathway, respectively.…”

“…Caspases (cysteinyl aspartate-specific proteases) are a family of proteases that play an important role in apoptosis. 36 Caspase-3 is the most critical apoptosis-executing protease in the process of apoptosis and can be activated by caspase-8 and caspase-9, which are related to the death receptor apoptosis pathway and mitochondria-dependent apoptosis pathway, respectively. According to the results in Figure 9F∼H, the activities of caspase-8 and caspase-9 in the codelivery group were both the highest, indicating that the apoptosis pathway of transfected cells was mediated by both death receptor and mitochondriadependent pathways.…”

“…The increase in intracellular ROS levels correlated with the magnitude of p53 protein expression and was associated with the induction of senescence or apoptosis in normal and cancer cells . ROS is both an upstream signal that triggers p53 activation and a downstream factor that mediates apoptosis. , Therefore, synergy between the p53 gene and PDT is a promising strategy for the cancer therapy. , …”

“…34,35 Therefore, synergy between the p53 gene and PDT is a promising strategy for the cancer therapy. 36,37 Chlorin e6 (Ce6), a second-generation PDT drug used in clinical practice, is a photosensitizer with near-infrared fluorescence emission and a high quantum yield of singlet oxygen. 38,39 Due to its low dark toxicity and strong tissue penetration, it has been widely used in the treatment of various malignant tumors.…”

Natural Biopolymer-Based Delivery of CRISPR/Cas9 for Cancer Treatment

“…In another study, oxidized glutathione (GSSG)-crosslinked PEI (GP) was used to condense DNA to form the positively charged polyplexes, and then sodium alginate (SA) with negative charge was absorbed onto the surface via electrostatic interactions to form the tertiary complex [ 74 ]. As expected, modification of sodium alginate improved the transfection efficiency of the cationic nanoparticles by approximately 50 times as sodium alginate could promote the cellular uptake and DNA release from the nanocomplex.…”