Fig. 8

This diagram illustrates the sophisticated DDS designed to target the ER in chondrocytes, which is crucial for alleviating ER stress in OA. The left panel details the structure of ER-targeting scFv antibodies, which are conjugated with therapeutic genes to facilitate direct delivery to the ER, bypassing lysosomal degradation. The right panel outlines the targeting mechanism of ER-targeting ligands, which include sulfonyl ligands, chloride ligands, amphoteric ions, and nanoparticle ligands. These ligands interact with specific ER membrane proteins, such as the chloride pump, K⁺ channel, CCT, SRPR, and KDELR, to increase the ER-targeting ability of the DDS. The diagram highlights the potential of these ER-targeting strategies to restore chondrocyte ER homeostasis, thereby offering a promising approach for OA treatment. scFv single-chain fragment variable, CCT cytidylyltransferase, SPR signal recognition particle, SRPR signal recognition particle receptor, KDELR KDEL receptor