Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants.

摘要: Imidazoquinoline derivatives (IMDs) and related compounds function as synthetic agonists of Toll-like receptors 7 8 (TLR7/8) one is FDA approved for topical antiviral skin cancer treatments. Nevertheless, these innate immune system-activating drugs have potentially much broader therapeutic utility; they been pursued antitumor immunomodulatory agents more recently candidate vaccine adjuvants infectious disease. The broad expression profiles TLR7/8, poor pharmacokinetic properties IMDs, toxicities associated with systemic administration, however, are formidable barriers to successful clinical translation. Herein, we review IMD formulations that advanced the clinic discuss issues biodistribution toxicity hampered further development compounds. Recent strategies aimed at enhancing safety efficacy, particularly through use bioconjugates nanoparticle alter pharmacokinetics, biodistribution, cellular targeting, described. Finally, key aspects biology TLR7 signaling, such tolerance, may need be considered in new therapeutics discussed.