Supramolecular Integration of Multifunctional Nanomaterial by Mannose-Decorated Azocalixarene with Ginsenoside Rb1 for Synergistic Therapy of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints and is associated with autoantibodies that target various molecules including modified self-epitopes. The identification of novel autoantibodies has improved diagnostic accuracy, and newly developed classification criteria facilitate the recognition and study of the disease early in its course. New clinical assessment tools are able to better characterize disease activity states, which are correlated with progression of damage and disability, and permit improved follow-up. In addition, better understanding of the pathogenesis of RA through recognition of key cells and cytokines has led to the development of targeted disease-modifying antirheumatic drugs. Altogether, the improved understanding of the pathogenetic processes involved, rational use of established drugs and development of new drugs and reliable assessment tools have drastically altered the lives of individuals with RA over the past 2 decades. Current strategies strive for early referral, early diagnosis and early start of effective therapy aimed at remission or, at the least, low disease activity, with rapid adaptation of treatment if this target is not reached. This treat-to-target approach prevents progression of joint damage and optimizes physical functioning, work and social participation. In this Primer, we discuss the epidemiology, pathophysiology, diagnosis and management of RA.

The field of supramolecular chemistry focuses on the non-covalent interactions between molecules that give rise to molecular recognition and self-assembly processes. Since most non-covalent interactions are relatively weak and form and break without significant activation barriers, many supramolecular systems are under thermodynamic control. Hence, traditionally, supramolecular chemistry has focused predominantly on systems at equilibrium. However, more recently, self-assembly processes that are governed by kinetics, where the outcome of the assembly process is dictated by the assembly pathway rather than the free energy of the final assembled state, are becoming topical. Within the kinetic regime it is possible to distinguish between systems that reside in a kinetic trap and systems that are far from equilibrium and require a continuous supply of energy to maintain a stationary state. In particular, the latter systems have vast functional potential, as they allow, in principle, for more elaborate structural and functional diversity of self-assembled systems - indeed, life is a prime example of a far-from-equilibrium system. In this Review, we compare the different thermodynamic regimes using some selected examples and discuss some of the challenges that need to be addressed when developing new functional supramolecular systems.