ArticleMolecular therapy. Nucleic acids2018
Delivery Pathway Regulation of 3',3″-Bis-Peptide-siRNA Conjugate via Nanocarrier Architecture Engineering.
Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Splenic dendritic cell-targeting mRNA transfection of H-type ionizable lipid-based LNPs for enhancing tumor immunotherapy.Bioactive materials · 2026Article
- Survival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting.Autophagy · 2025Review
- Amphiphilic Polypeptides Obtained by Post-Polymerization Modification of Poly-l-Lysine as Systems for Combined Delivery of Paclitaxel and siRNA.Pharmaceutics · 2023Article
- Advanced Strategies for Overcoming Endosomal/Lysosomal Barrier in Nanodrug Delivery.Research (Washington, D.C.) · 2023Review
- Feasibility of cRGD conjugation at 5'-antisense strand of siRNA by phosphodiester linkage extension.Molecular therapy. Nucleic acids · 2021Article
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Authors and funding
9 authors.
Funding
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Abstract
Small interfering RNA (siRNA) has been continuously explored for clinical applications. However, neither nanocarriers nor conjugates have been able to remove the obstacles. In this study, we employed a combined nanochemistry strategy to optimize its delivery dilemma, where different interactions and assembly modes were cooperatively introduced into the forming process of siRNA/lipids nanoplexes. In the nanoplexes, the 3',3″-bis-peptide-siRNA conjugate (pp-siRNA) and gemini-like cationic lipids (CLDs) were employed as dual regulators to improve their bio-behavior. We demonstrated that the "cicada pupa"-shaped nanoplexes of MT-pp-siRNA/CLDs (MT represented the mixed two-phase method) exhibited more compact multi-sandwich structure (∼25 layers), controllable size (∼150 nm), and lower zeta potential (∼22 mV) than other comparable nanoplexes and presented an increased siRNA protection and stability. Significantly, the nanoplex was internalized into melanoma cells by almost caveolae-mediated endocytosis and macropinocytosis (∼99.46%), and later reduced/avoided lysosomal degradation. Finally, the nanoplex facilitated the silencing of mRNA of the mutant B-Raf protein (down by ∼60%). In addition, pp-siRNA had a high intracellular sustainability, a significantly prolonged circulating time, and accumulation in tumor tissues in vivo. Our results have demonstrated that the combined approach can improve the intracellular fate of siRNA, which opens up novel avenues for efficient siRNA delivery.
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