Context <p>Lupus nephritis (LN) is a severe autoimmune kidney disorder associated with systemic lupus erythematosus and occurs predominantly in women. Monocyte chemoattractant protein-1 (MCP-1/CCL2) plays a critical role in the pathogenesis of LN by promoting monocyte recruitment and sustaining renal inflammation. Targeting MCP-1 therefore represents an important therapeutic strategy for reducing immune-mediated kidney damage. In this study, a nanoinformatics-guided approach was used to design folic acid–functionalized fullerene nanostructures as potential MCP-1 inhibitors. Folic acid was selected as a targeting ligand due to its affinity for folate receptors expressed on activated macrophages, while hydroxylated fullerenes provide a stable nanocarrier capable of strong hydrophobic interactions. Molecular docking revealed that the folic acid–fullerene conjugate showed significantly improved binding affinity toward MCP-1 (docking score − 249) compared with folic acid alone (− 140). Interaction analysis demonstrated that the fullerene core forms strong hydrophobic contacts within the MCP-1 binding cavity, while the folic acid moiety contributes hydrogen bonding and electrostatic interactions that stabilize the complex. Toxicity prediction indicated an overall low toxicity profile, suggesting that folic acid–functionalized fullerenes may serve as promising targeted nanotherapeutic candidates for lupus nephritis.</p> Computational methods <p>The three-dimensional structure of MCP-1 (PDB ID: 1DOM) was retrieved from the Protein Data Bank and prepared for docking studies. Folic acid was obtained from the PubChem database and converted into three-dimensional format. Toxicity prediction was carried out using the ProTox-3 web server. The fullerene (C₆₀) nanostructure was modeled and hydroxylated using the Atomic Simulation Environment (ASE), followed by conjugation with folic acid using Avogadro 2 and structural optimization. Molecular docking of folic acid and the folic acid–fullerene conjugate with MCP-1 was performed using the HDOCK server. Protein–ligand interactions were analyzed using BIOVIA Discovery Studio Visualizer. Pharmacokinetic properties were evaluated using the SwissADME platform. Molecular dynamic simulations were conducted using the Desmond module of Schrödinger to assess the stability and dynamic behavior of the receptor–ligand complex.</p>