Remant KC , Mohammad Nasrullah , Gurkirat Sandhu , Cezary Kucharski , Afsaneh Lavasanifar , Hasan Uludag
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引用次数: 0
Abstract
Conventional therapeutic approaches often struggle to address “undruggable” or intracellular targets, limiting their effectiveness in treating critical diseases. RNA interference (RNAi), particularly through the delivery of short interfering RNAs (siRNAs), has emerged as a promising alternative. In this study, we evaluated the potential of a series of cationic lipopolymers, including ALL-Fect, Leu-Fect, and Prime-Fect, for delivering siRNAs targeting CDC20, Survivin, and STAT5 in lung cancer cell models. These polymers exhibited strong siRNA binding (BC50: 0.17 ± 0.04 to 1.67 ± 0.31) and dissociation (DC50: 57.9 to 13.6 U/mL) properties, forming nanoparticles with ζ-potential of −15 to +23 mV, and particles sizes of 150 to 400 nm suitable for efficient cellular uptake, achieving over 75 % FAM-positive cell populations in lung cancer cells. Remarkably, these complexes demonstrated significant cell killing effects with specific siRNAs even at a low siRNA concentration (20 nM), with maximal effects observed at a polymer/siRNA ratio of 5:1 ratio and 40 nM siRNA concentration, resulting in over 75 % cell killing. The performance of lipid nanoparticles (LNPs) for the delivery of the specific siRNAs was minimal compared to the lipopolymeric carriers under similar conditions. These findings underscore the potential of lipopolymers as safe and effective non-viral vectors for siRNA-based lung cancer therapeutics.
期刊介绍:
Biomaterials Advances, previously known as Materials Science and Engineering: C-Materials for Biological Applications (P-ISSN: 0928-4931, E-ISSN: 1873-0191). Includes topics at the interface of the biomedical sciences and materials engineering. These topics include:
• Bioinspired and biomimetic materials for medical applications
• Materials of biological origin for medical applications
• Materials for "active" medical applications
• Self-assembling and self-healing materials for medical applications
• "Smart" (i.e., stimulus-response) materials for medical applications
• Ceramic, metallic, polymeric, and composite materials for medical applications
• Materials for in vivo sensing
• Materials for in vivo imaging
• Materials for delivery of pharmacologic agents and vaccines
• Novel approaches for characterizing and modeling materials for medical applications
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