Palmitic acid-modified bovine serum albumin nanoparticles target scavenger receptor-A on activated macrophages to treat rheumatoid arthritis

• Published in: Biomaterials Vol. 258; p. 120296
• Main Authors: Gong, Ting, Tan, Tiantian, Zhang, Pei, Li, Haohuan, Deng, Caifeng, Huang, Yuan, Gong, Tao, Zhang, Zhirong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2020
• Subjects: Animals; Arthritis, Rheumatoid - drug therapy; Drug Carriers - therapeutic use; Macrophages; Nanoparticles; Palmitic Acid; Palmitic acid modified BSA; Prolonged circulation time; Rats; Receptors, Scavenger; Rheumatoid arthritis; Safety; Serum Albumin, Bovine - therapeutic use; Targeting scavenger receptor-A; Prolonged circulation time; Targeting scavenger receptor-A; Safety; Palmitic acid modified BSA; Rheumatoid arthritis
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2020.120296

Palmitic acid-modified bovine serum albumin (PAB) was synthetized and found to own remarkable scavenger receptor-A (SR-A) targeting ability in vitro and in vivo, through which activated macrophages took up PAB nanoparticles (PAB NPs) 9.10 times more than bovine serum albumin nanoparticles (BSA NPs) and PAB NPs could delivery anti-inflammatory drugs celastrol (CLT) to inflamed tissues more effectively than BSA NPs. Compared with chondroitin sulfate modified BSA NPs targeting activated macrophages via CD44, PAB NPs show a more prominent targeting effect whether in vivo or in vitro. And PAB also demonstrated excellent biosafety compared to maleylated BSA, a known SR-A ligand that was lethal in our study. Furthermore, in adjuvant-induced arthritis rats, CLT-PAB NPs significantly improved disease pathology at a lower CLT dose with high safety, compared with CLT-BSA NPs. In addition, compared with the existing ligands with SR-A targeting due to strong electronegativity, the enhanced electronegativity and introduced PA are both important for the SR-A targeting effect of PAB. Therefore, PAB provides a novel direction for the treatment of rheumatoid arthritis and design of new ligands of SR-A.