Cationic solid lipid nanoparticles loaded by integrin beta 1 plasmid DNA attenuates IL-1 beta-induced apoptosis of chondrocyte

Zhao, YJ; Chen, HW; Wang, L; Guo, ZY; Liu, SJ; Luo, SM

Abstract

Aging-related inflammation is tightly linked with the development of osteoarthritis (OA). As the pro inflammatory cytokine, IL-1 beta has been associated with physical dysfunction and frailty. It is still elusive whether and how IL-1 beta blockade improves the outcome of OA. Here we develop a cationic solid lipid nanoparticles (SLNs) system that effectively mediate non-viral delivery of plasmid DNA (pDNA) into cells. Compared with other DNA transfer technologies including lipofetamin 2000, SLNs-pDNA system is less toxic and exerts identical effectiveness on DNA transfer. Loaded with integrin beta 1 overexpression pDNA, the SLNs-pDNA mainly localized in cytoplasm and enforced expression of integrin beta 1 in rat chondrocytes. Moreover, upon exposure to IL-1 beta stimulation, SLNs-pDNA treatment attenuates the apoptosis rat chondrocytes and augments tissue repair. Our data thus demonstrate that SLNs-pDNA functions as a potential therapeutic nanomedicine in the treatment of osteoarthritis.

Keywords: osteoarthritis; integrin beta 1; cationic solid lipid nanoparticles; chondrocytes

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Liposomes for DNA/RNA Delivery

Interleukin-1β (IL-1β) plays a pivotal role in inflammatory responses, particularly in osteoarthritis, where it induces chondrocyte apoptosis, leading to cartilage degradation. DNA-loaded cationic solid lipid nanoparticles (SLNs) emerge as a promising therapeutic approach to counteract this process. These nanoparticles are designed to deliver anti-apoptotic genes or gene silencing constructs directly into chondrocytes. The cationic nature of SLNs enhances cellular uptake by facilitating binding to the negatively charged cell membranes. Once inside the cell, the DNA cargo can modulate gene expression to inhibit apoptotic pathways activated by IL-1β. This targeted delivery system not only improves the stability and bioavailability of the genetic material but also minimizes off-target effects, making it a highly effective strategy. Studies have shown that DNA-loaded cationic SLNs can significantly reduce chondrocyte apoptosis, thus potentially halting the progression of osteoarthritis and promoting cartilage repair.