Precision design of engineered nanomaterials to guide immune systems for disease treatment

•We review the recent advances in molecular pathways of ENM-induced immune responses •We outline how ENMs' properties impact ENMs' contact with immune systems •We discuss how to design ENM properties for effective immunomodulation therapy •We discuss the opportunities of the next-stage immunological nanobiology research Engineered nanomaterials (ENMs) are widely used in industrial, commercial, and medical fields due to their unique physicochemical properties and diverse functional advantages. Human exposure or direct contact with ENMs via various routes, including dermal, inhalation, and systemic administration, may allow ENMs to interact with immune systems, leading to immunostimulation or immunosuppression outcomes depending on antigen properties. The actions of various immunological responses and how ENMs' intrinsic properties impact immune responses are fascinating but under-investigated. Herein, we systemically review state-of-the-art advances in various molecular mechanisms of ENM-induced immunological responses to outline the critical roles of material properties on immunity. Through the growing awareness of nano quantitative structure-activity relationship (QSAR), we further conceptualize how to utilize ENMs’ immunomodulatory properties to develop safe, precise, and effective immunomodulation strategies based on high throughput and predictive discovery paradigms. We also discuss the challenges and opportunities for clinical translation using nano-enabled immune modulation for disease treatment. Engineered nanomaterials (ENMs) are widely used in industrial, commercial, and medical fields due to their unique physicochemical properties and diverse functional advantages. Human exposure or direct contact with ENMs via various routes, including dermal, inhalation, and systemic administration, may allow ENMs to interact with immune systems, leading to immunostimulation or immunosuppression outcomes depending on antigen properties. The actions of various immunological responses and how ENMs' intrinsic properties impact immune responses are fascinating but under-investigated. Herein, we systemically review state-of-the-art advances in various molecular mechanisms of ENM-induced immunological responses to outline the critical roles of material properties on immunity. Through the growing awareness of nano quantitative structure-activity relationship (QSAR), we further conceptualize how to utilize ENMs’ immunomodulatory properties to develop safe, precise, and effective immunomodulation strategies based on high throughput and predictive discovery paradigms. We also discuss the challenges and opportunities for clinical translation using nano-enabled immune modulation for disease treatment.