Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications

Innate immunity is the first line of defense against invading pathogens. Innate immune cells can recognize invading pathogens through recognizing pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs). The recognition of PAMPs by PRRs triggers immune defense mechanisms and the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. However, sustained and overwhelming activation of immune system may disrupt immune homeostasis and contribute to inflammatory disorders. Immunomodulators targeting PRRs may be beneficial to treat infectious diseases and their associated complications. However, therapeutic performances of immunomodulators can be negatively affected by (1) high immune-mediated toxicity, (2) poor solubility and (3) bioactivity loss after long circulation. Recently, nanocarriers have emerged as a very promising tool to overcome these obstacles owning to their unique properties such as sustained circulation, desired bio-distribution, and preferred pharmacokinetic and pharmacodynamic profiles. In this review, we aim to provide an up-to-date overview on the strategies and applications of nanocarrier-assisted innate immune modulation for the management of infections and their associated complications. We first summarize examples of important innate immune modulators. The types of nanomaterials available for drug delivery, as well as their applications for the delivery of immunomodulatory drugs and vaccine adjuvants are also discussed.