Folate-modified nanodelivery platform loaded with triptolide for targeted synergistic photothermal therapy of macrophages to alleviate rheumatoid arthritis

Rheumatoid arthritis (RA) is treated mainly with oral medication. However, the use of disease-modifying antirheumatic drugs (DMARDs) through the oral route is restricted because of low bioavailability, poor absorption, hepatotoxicity and serious adverse effects, requiring the investigation of alternative delivery methods. Targeted nanodelivery system loaded with Triptolide (TPL) for intra-articular injection presents a promising solution, avoiding the toxic side effects arising from the nonspecific effects of free drug molecules. Nevertheless, current nanodelivery systems typically lack extended therapeutic periods and involve complex synthesis processes. Furthermore, a single treatment approach often fails to yield remarkable outcomes. Herein, we develop a multifunctional drug delivery system (DDS) consists of gold nanoparticles (AuNPs) and hydroxyapatite (HAP) mesoporous hollow nanoparticles loaded with folic acid (FA) and TPL, called FA-TPL@HAP@AuNPs (FA-THA). These nanoparticles use HAP as a base, encapsulate AuNPs for photothermal therapy (PTT), and are coated with FA and TPL on their surface. The mesoporous structure of the HAP nanoparticles acts as a storage space for TPL, while the FA component ensures that the DDS selectively targets inflamed joint areas to kill inflammatory cell through PTT. HAP mesoporous hollow microspheres ensure good biocompatibility and extend drug sustained release. Owing to its optimized TPL release behavior and significant PTT, FA-THA exhibits potent anti-inflammatory effects in adjuvant-induced arthritis (AIA) rats following intra-articular injection. The FA-THA system, a multifaceted drug delivery platform, exhibited high biocompatibility and therapeutic outcomes, making it become a promising candidate for the treatment of RA.