Cartilage-targeting mRNA-lipid nanoparticles rescue perifocal apoptotic chondrocytes for integrative cartilage repair

Harnessing Nanomedicine for Cartilage Repair: Design Considerations and Recent Advances in Biomaterials

“…Gene therapy enabled by these nucleic acid-loaded lipid NPs for cartilage repair serves a number of purposes: (1) promoting the expression of proteins conducive to cartilage repair, such as cytokines that promote cartilage regeneration, ,, anti-inflammatory cytokines, and chemokine proteins that recruit stem cells; (2) inhibiting undesirable expression of certain proteins including type I collagen and tumor necrosis factor-α (TNF-α); (3) co-delivering the aforementioned two types of nucleic acids. − For instance, positively charged lipid NPs were able to encapsulate mRNA that encoded IGF-1. This NP complex was capable of reducing chondrocyte apoptosis, thereby contributing to integrative cartilage repair . Solid-lipid NPs were able to encapsulate TNF-α small interfering RNA (siRNA) with an efficiency up to 90%, and a <5% burst release of siRNA effectively cured arthritis .…”

“…Furthermore, HA-binding peptides were conjugated to the surface of the cartilage via heterobifunctional PEG chains, which facilitated the localization of HA on the cartilage surface and enhanced cartilage lubrication . Recently, CAQK, a peptide sequence previously used in a neural drug delivery system, was introduced into lipid NPs for aggrecan targeting …”

“…The advancement in nanotechnology has led to the development of various nanoscale delivery systems for cartilage repair. These delivery systems are typically characterized by their biodegradable, nontoxic, and biocompatible properties. ,, They hold great promise for site-specific delivery and controlled release of active compounds, thereby achieving good therapeutic outcomes. Importantly, the dense ECM that forms the cartilage environment necessitates the ability to penetrate deep into cartilage and maintain a high retention rate by these nano delivery systems.…”